Gin & Tonic – Part 2 – Malaria, fever and alternating fever and its treatment with quinine wine

In the second part of this series, we turn to the medicinal uses of quinine. We report on malaria, fever and alternating fever and its treatment with quinine wine.

Malaria

The term malaria is derived from the Italian and means “bad air”. ^[2-32] The nature of malaria was not understood for a long time. ^[2-11] It was not until 1880 that Charles Louis Alphonse Laveran recognised the connection between malaria and parasites in the blood. For this he received the Nobel Prize for Medicine in 1907. ^[2-34] Ronald Ross discovered that mosquitoes transmit the parasite and was awarded the Nobel Prize for Medicine in 1902. ^{[2-36] [2-34]} Malaria parasites existed 30 to 40 million years ago. They were found encased in amber. ^[2-25]

Nowadays one may think that malaria is a tropical disease, but until recently it was also present in Europe, as far north as the Arctic Circle and in Western Europe. ^{[2-14] [2-25]} For example, Horace Walpole wrote in 1740: “there is a horrid thing called the malaria, that comes to Rome every summer, and kills one.” ^[2-32]

Malaria was widespread not only in southern but also in central Europe until the middle of the 20th century. ^[2] Malaria and tropical diseases were also a serious problem in the colonies. For example, among British troops in Sierra Leone between 1819 and 1836, an average of 48% of soldiers died from tropical diseases. On William Bolt’s expedition to Mozambique, 132 out of 152 European participants died. On Lander-Laird’s Niger expedition in 1832, the figure was 40 out of 49. ^[2-46] Although cinchona bark was occasionally used by the British Navy from the late 18th century, the use of quinine to prevent malaria was not formally recognised until 1854, when William Balfour Baikie led a Niger expedition. Each of the participating Europeans took a daily ration and all returned alive. ^[2-48]

Gin Punch as medicine

Gin Punch was also used to treat malaria and similar diseases. We do not want to go into detail here, as we have already done so in our article on Gin Punch. At this point, a summary may suffice: Gin Punch was used to treat malaria and other similar diseases, also together with cinchona bark or quinine wine.

There are also examples of gin punch being prescribed together with cinchona bark in an 1848 book on the diseases of India. ^{[12-286] [12-287]} This is reminiscent of taking Gin & Tonic, for this is after all a kind of Gin Punch to which quinine has been added. But before we can look at Gin & Tonic in more detail, we must turn to quinine wine.

Quinine and wine as medicine

Let’s remember: quinine is highly soluble in alcohol, but poorly soluble in water, and acid aids solubility. Perhaps quinine was preferably dissolved in wine, since wine contains acid as well as alcohol? Nevertheless, it seems that wine was not exclusively used to dissolve quinine. In an article published in 1841 in The English Journal, entitled “Summer Tourists”, one complains about a trip to Holland where one has to drink genever and quinine to keep malaria away: “I do notlike sipping tea at a lust huis to the music of frogs in the green moats around keeping out the miasma with eternal doses of quinine and geneva.” ^[2-93]

So let’s look at the sources chronologically, especially in the 19th century, to understand with which spirit quinine was taken, how much of it, and for what purpose.

We have already pointed out that Robert Talbor’s English Remedy was made with wine and quinine at the end of the 17th century. However, this recipe contained other ingredients.

1734

In a publication from the year 1734 we have found instructions for the production of a quinine wine. It is prepared from “Peruvina bark”, i.e. cinchona bark, and wine, and it is stated that this mixture can cure some types of alternating fever. ^{[15-230] [15-231] [15-232]}

Numerous medical works subsequently refer to “bark and wine”. Let’s skip the mentions of the next years and jump directly to the year 1755.

1755

In 1755, scurvy on board ships is written about: “The difficulty of treating patients as they ought on board ships, makes it scarce possible to stop the disease when it is once begun; it is therefore much better to endeavour at its prevention, and thus save the lives of many brave men, and much ineffectual trouble: … the ship kept as clean as possible, the sailors obliged to keep themselves dry as much as duty will permit, by changing clothes, and even indulged in spirituous liquors, though not to inebriating, brandy and water being allowed in the place of beer; every man on board obliged to drink an infusion of cortex peruvianus, or in its place oak bark, in which is dropt elixir of vitriol, every morning as regularly as any other duty on board;” ^{[7-191] [7-192]}

In this text, what has already been explained becomes visible. Cinchona bark, here called Peruvian bark or cortex peruvianus, is more soluble in alcohol than in water, and the solubility is improved in an acidic environment, which is apparently why vitriol was added. Vitriol is a trivial name for salts of sulphuric acid, which were also called vitriol oil. ^[41]

1775

In 1775, a book was published with the title “Observations on the diseases of the army“. It writes about the long persistence of the disease and the relapses of “marsh-fever”, “against which there was no security, unless the patient took an ounce of the powder once every ten or twelve days, throughout the autumn. The most effectual method to make a soldier continue the Bark, is to mix it with equal parts of brandy and water *. … * I have since observed, that the surest way of preventing a relapse, in those who unwillingly return to the use of the Bark, is, to give four or five ounces in powder, as fast as the patient can be prevailed upon to take it: this quantity he may finish in six or seven days.” ^[6-210]

1784

In 1784, a letter is published in which the author reports what happened to him on arrival at the Banana Islands, located off Sierra Leone in West Africa. ^{[4] [5-186] [5-188]} He notes: “In about five days after my arrival at the Bananas, and by the time my little cargo was landed and secured, I was compelled to avail myself of the Doctor’s goodness, being attacked by a military fever; of which, by following his prescription pretty closely, with some reference to my other medical information, I got very well in a few days †. … † In one of the Doctor’s affectionate letters he observes — “The diseases most to be dreaded on the coast of Africa, are fevers and fluxes. To prevent these as much as possible, in case of perceiving any severish symptoms, … . It will then be necessary, in most of the fevers on the coast of Africa, to have recourse to the bark, in large quantities, during the interval of the fits: an ounce may be taken, either in a little brandy and water, or red port and water, between the fits; half an ounce between the next two fits; and so on till the fever goes off. …”” ^[5-188]

We can see from the examples selected here that cinchona bark was not only dissolved in distillates but also in wine. At the same time, we can see that the amount of bark to be ingested was considerable. Let us skip the further discoveries of the following years by almost forty years. At that time, it was possible to extract the actual active ingredient from the cinchona bark.

1823

A book published in 1823 by the Royal College of Surgeons of England, a translation from the French, describes the two alkaloids that could be extracted from cinchona bark. This source is important because it also gives information on how to dose them. A distinction was made between cinchonine and quinine. The former was obtained from the grey bark of Cinchona condaminea. The yellow bark of Cinchona cordifolia was used to extract quinine. ^[27-46]

“Cinchonine is … soluble only in 700 parts of cold water. The latter circumstance occasions its little sapidity. If it be dissolved in alcohol, or rather in an acid, its flavour is a powerful bitter, which exactly resembles that of the grey bark. … Cinchonine … forms more or less soluble salts with acids. … The sulphate and acetate of cinchonine are used in medicine. The first of these salts is very soluble in water; the second much less so, but an excess of acid dissolves it with tolerable facility.” ^[27-46]

Quinine, on the other hand, is “as little soluble in water as the cinchonine; it is much more bitter, however, to the taste. Its salts also are in general more bitter; … Quinine is very soluble in ether, while cinchonine is very little so. This difference not only serves to distinguish these cases, but also to separate them when united.” ^[27-47]

One then describes the production and properties:- “The sulphate of quinine obtained in this way, is in the form of white crystals, which are entirely soluble in water; little so, however, in cold water, but more so in boiling, and especially in weakly acidulated water.” ^[27-48]

The benefits of the extracts are then discussed:

“Patients often die of malignant fevers, because they cannot swallow the necessary quantity of the bark in powder.” ^[27-51]

“The sulphates of quinine and cinchonine are the preparations most commonly employed. From one to ten grains (gr. 0.82 to gr. 8.20 T.) of either of them may be given in the twentyfour hours. Some physicians have thought it necessary to carry the dose much higher than this, but in general the success has not answered to their expectations; several patients, indeed, have experienced somewhat severe accidents …” ^[27-52]

Recipes for quinine syrup, quinine wine and a quinine tincture then follow. Of particular interest here is the quinine wine: “Wine of Quinine. Take of Good Madeira wine 1 litre (oz. 32.104 T.) Sulphate of quinine 12 grains (gr. 9.84 T.) This preparation may be made with Malaga wine, or even with vin ordinaire.” ^{[27-53] [27-54]} If cinchonine is used, the recipes are similar, but more cinchonine is used than quinine. ^[27-55]

1824

The Gentleman’s Medical Vade-mecum”, published in 1824, describes how to treat fever or alternating fever: “use a tablespoonful of the quinine mixture, three or four times a day; if it cannot be procured, take as large doses of Peruvian bark as the stomach will bear; im addition to this, endeavour during the cold fit to bring on the hot one, as speedily as possible, by warm drinks, bladders or bottles filled with warm water applied to the soles of the feer and the stomach. Weak whisky punch answers this purpose very well, it also is of use by inducing sweat, when the hot stage is formed.” ^{[28-25] [28-26] [28-27]}

The recipe for the quinine mixture is published at the end of the book. However, it is recommended here to take one tablespoon of it every hour. In the preparation of this mixture one uses: “Sulphate of Quinine gr. xiii | Gum Arab. powdered, dr. i | Loaf Sugar oz. ss | Water oz. vi | Ess. of Pepermint, gutt. v | A tablespoonful every hour. Shaking the bottle well before it is poured out.” ^[28-229] Where: gr – grain; dr – drachm or three scruples; oz – 1 ounce or eight drachms; gutt. – drops; ss – half of the quantity that precedes it. ^[28-229]

This treatment is also recommended for other types of fever or typhus. ^{[28-28] [28-31]} Quinine sulphate is also said to help against neuritis of the face. ^{[28-117] [28-118]} The use of quinine sulphate is also discussed in more detail in connection with typhus and other fevers: “Great reliance is now placed upon the sulphate of quinine, which may be taken in doses of two or three grains, four times a day, dissolved in a little gum arabic tea, or in pills.” ^[28-33]

At the same time, alcoholic beverages such as wine, brandy or porter are prescribed. ^[28-33] The amount of quinine to be used varies, however. It is also written that one should take less in case of indigestion: “The new preparation of bark, called sulphate of quinine, promises to be of much use in the complaint of which we are speaking. It must be taken to the amount of four grains a-day, in divided doses, either dissolved in water, or in pills. Weak spirits and water, or a single glass of sound old Madeira, may be taken at dinner, but all malt liquors should be avoided.” ^[28-61]

Sigmund Graf states in his work on fever barks published in 1824: “The simplest way to use fever bark is in the powdered state. … Among all preparations, however, the tinctures deserve preference. For it has been proved by all available analyses that they contain the active substance bound to an acid, together with a small quantity of colouring and fatty matter; but on the other hand are free from gum, starch flour, Chinese red, etc.. Since alcohol of a greater specific gravity than these alkalis dissolves much more easily than water, it is naturally preferable to the latter. The so-called China wines are therefore closest to the tinctures in their effectiveness and are all the better the more spiritual the wine used.” ^{[18-103] [18-105] [18-106]}

–  “Die einfachste Art die Fieberrinde anzuwenden, ist der gepulverte Zustand. … Unter allen Zubereitungen verdienen jedoch die Tincturen den Vorzug. Denn nach allen vorliegenden Analysen ist es erwiesen, dass sie den wirksamen Stoff, an eine Säure gebunden, nebst einer geringen Menge färbender und fetter Materie enthalten; dagegen aber von Gummi, Stärkmehl, Chinaroth u.s.w. frey sind. Da Alkohol von einem grössern specifischen Gewichte als diese Alkalien viel leichter auflöset als wasserhaltiger, so ist er natürlich diesem vorzuziehen. Die sogenannten China-Weine stehen daher den Tincturen in ihrer Wirksamkeit am nächsten und sind um so besser, je geistiger der angewendete Wein war.” ^{[18-103] [18-105] [18-106]}

The following is a collection of recipes from various publications. By way of example, we mention here: “In France, where the active constituents of fever bark first became known, the following preparations have been suggested for use: … Wine with quinine. Take 1 pint *) of good Madera wine and dissolve 12 grains of sulphuric quinine in it.” ^[18-109]

– „Man hat auch in Frankreich, wo die wirksamen Bestandtheile der Fieberrinden zuerst näher bekannt wurden, folgende Präparate in Anwendung zu bringen vorgeschlagen: … Wein mit Chinin. Man nimmt 1 Pinte *) guten Madera-Wein und löset in selber 12 Gran schwefelsauren Chinins auf.“ ^[18-109]

This is an important text because it informs us not only that wine with quinine was known and used in France, but also how much quinine per litre should be used.

1829

In 1829, another recipe for quinine wine was published. For this, nine grains of quinine sulphate are used for two pounds of Madeira wine. ^{[29-153] [30] [31]}

1830

In 1830 it is stated: “One prepares a quinine alcoholate by dissolving six grains of sulphuric quinine in an ounce of alcohol. As Magendie rightly points out, one must prefer the sulphuric quinine to the pure quinine, because the alcohol, by combining with the water, would drive the alkaloid, which would then not dissolve. The quinine wine is combined with the sulphuric quinine in the ratio of twelve grains of sulphuric quinine to two pounds of Madera or Malaga wine. The quinine syrup is far stronger; according to Magendie’s forms, it contains two grains of sulphuric quinine per ounce. The syrup, the wine and the alcoholate of quinchonine are composed in the same way, except that one takes a third more of the sulphuric quinchonine, because its effect, as we have seen, is generally far weaker than that of the sulphuric quinine.” ^[10-133]

– “Man bereitet ein Chinin-Alkoholat, indem man sechs Gran schwefelsaures Chinin in einer Unze Alkohol auflösen lässt. Man muss, wie Magendie mit Recht bemerkt, das schwefelsaure Chinin dem reinen Chinin vorziehen, weil der Alkohol, indem er sich mit dem Wasser verbindet, das Alkaloïd fahren lassen würde, welches sich dann nicht auflöst. Man verbindet den Chininwein mit dem schwefelsauren Chinin in dem Verhältnisse von zwölf Gran schwefelsauren Chinins auf zwei Pfund Madera- oder Malagawein. Der Chininsyrup ist weit stärker; er enthält nach Magendie’s Formulare zwei Gran schwefelsaures Chinin in der Unze. Der Syrup, der Wein und das Alkoholat des Chinchonins sind auf die nämliche Weise zusammengesetzt, nur nimmt man vom schwefelsauren Chinchonin einen Dritttheil mehr. weil seine Wirkung, wie wir gesehen haben, im Allgemeinen weit schwächer als die des schwefelsauren Chinins ist.” ^[10-133]

1840

In 1840, it is written that one should prepare a tincture from 6 grains of sulphuric quinine and an ounce of alcohol. Then it continues: “If one adds a pint of wine to 2 ounces of this tincture, one has a good quinine wine. Use as a tonic, especially in cases of tendency to intermissions in the condition; slackness of the digestion; scrofula.” ^[11-247]

– “Setzt man 2 Unzen dieser Tinctur eine Pinte Wein zu, so hat man einen guten Chininwein. Anw. als Stärkungsmittel, besonders bei Neigung zu Intermissionen im Befinden; Schlaffheit der Verdauung; Scrofeln.” ^[11-247]

Scrofula is a historical name for a skin disease that was most likely skin tuberculosis. ^[3]

1843

In 1843, an account of a journey to the Niger was published. It states: “Wine and quinine may be given to the men occasionally in lieu of wine and bark, and its issue may be extended to the whole crew when thought desirable by the surgeon.” ^[32-22]

It is also written: “and quinine dissolved in wine was frequently administered in ten-grain doses to all hands.” ^[32-176]

“I would, however, recommend the daily use of quinine, with a good diet, and a moderate allowance of wine” ^[32-188]

1844

In 1844, quinine wine is made by mixing a pint of good Madeira wine with 16 grains of quinine sulphate, and a full wine glass of this is taken twice a day. ^[33-261]

An alternative recipe uses 1 scruple of quinine, 10 grains of citric acid, 1 ounce of distilled water and 11 ounces of sherry wine. This is to be taken two to three times a day, one to two teaspoonfuls in a small wine glass filled with cold water and drunk. ^[33-262]

1852

In connection with an expedition in 1852 to the Wellington Channel, a strait in the Canadian Arctic Archipelago, ^[37] the ship’s captain proposes for the maintenance of health in the polar climate: “Loss of appetite, from want of tone and energy in the digestive organs, sometimes follows the effects of a long and tedious winter in some constitutions. A wineglassful of quinine wine, given twice a day, is the most efficacious remedy in these cases; it is best prepared by dissolving about a scruple of quinine, with the same quantity of citric acid, in a wineglassful of water, and then adding it to a bottle of wine, either port ot sherry, as may best suit the occasion.” ^[36-47]

1853

The recipe for Collier’s quinine wine, published in 1853, reads: “Disulphate of quinine, 18 grains, citric acid, 15 grains, orange wine, 24 oz. Mix the powders with a little wine, and add the rest. Tonic, stimulant.” ^[35-47]

It is also written: “QUININE, SULPHATE OF, L. – A crystallized salt, prepared from yellow bark. Soluble in water, especially if mixed with an acid. … Disulphate of quinine is given in ague, rheumatism, and tic-doloreux … Dose: 1 to 10 grains.” ^[35-176]

1854

In 1856, an expedition to the Niger and its tributary Benue in 1854 was reported. Quinine was used there, and it is reported: “Being now fairly in the river, we commenced giving, morning and evening, to all Europeans on board, two-thirds of a glass of quinine wine, which contained about five grains of quinine, believing that this would act as a prophylactic or preventive, while exposed – as every one must be while in the Delta – to the influence of malaria.” ^[39-34]

1857

The second edition of The Seaman’s Medical Friend, published in 1857, states: “No. 10. – SULPHATE OF QUININE. This powerful and permanent tonic medicine has quite superseded the use of Peruvian Bark. It is used in the treatment of ague and other intermittent disorders, and as a tonic to strenghten the system generally. Dose, as a tonic, one or two grains three times a day; in ague, two or five grains every four hours. If headache, giddiness, and sickness come on, the Quinine should be stopped. It may be given in pills, as a powder, or dissolved in water, to which a little Elixir of Vitriol (No. 53) – twice as many drops as there are grains of Quinine – has been added, as it will not dissolve in water alone.” ^[40-20]

Vitriol is a salt of sulphuric acid. ^[41] This is an interesting find. Here the quinine sulphate is dissolved in water by the sailor. Remember: quinine is poorly soluble in water; which is presumably why vitriol elixir is to be added at the same time to improve solubility. Wine is not mentioned here, perhaps because it was not so readily and generally available to the ordinary sailor?

1862

In 1862, W. J. Moore discusses health in the tropics, with special reference to Europeans in India. He comes to the following conclusion about malaria prophylaxis: “It has long been a standing rule in the navy, enjoined by Art. 9 of the ‘Surgeon’s Instructions,’ that when men are sent on shore in tropical climates the surgeon is to recommend for each man, previous to leaving the ship, quinine and wine, and the same on return, if necessary. Dr. Bryson (‘Med. Times and Gazette,’ January, 1854) gives the reports of twelve medical officers, showing the good effects of the prophylactic on the South African station, the ratio of deaths falling during the year from an enormous figure to 6.9 per 1000. I can also bear witness to the power of quinine as a preservative against fevers in the Persian Gulf, as exemplified by the exemption of seamen taking the alkaloid from malarious disease. Hence I would recommend that, on all occasions when soldiers are exposed to malarious influence or obliged to be located in known miasmatous localities, and during the malarious months, that the preservative effects of quinine wine should be taken advantage of, by administering it to the men.” ^[48-232]

The author continues: “The great importance of introducing the cinchona plant into India, has become more and more apparent of late years owing to the increased demand for its invaluable alkaloid quinine. Dr. Ewart (“A Review of the Treatment of Tropical Diseases;” ‘Ind. An. Med. Sci.,’ vol. xiv) shows that the expense of this agent alone during 1857-8, for the Calcutta Presidency, amounts to £12,408, besides the cost of thousands of pounds on cinchona bark, und upwards of one hundred pints of liquor amorphus quinae. In Madras, during the same period, 267 lbs. of quinine was used, costing £1,284. The Dutch have already succeeded in growing the cinchona plant in their eastern possessions, and the introduction into India was commenced under the fostering care of Lord Stanley, when Secretary of State. Recent accounts show that there is every probability of the cinchona plant being naturalized on our Indian ranges – an event which will be trebly beneficial, relieving the state of considerable expense, affording a wide field of occupation for European colonists, and rendering the antiperiodic cheaper and more available to all classes resident in India.” ^{[48-283] [48-284]}

The aforementioned Lord Stanley headed the Colonial Department in 1858 and 1859. ^[49]

1863

The health of the navy on the African west coast is reported on in an annual review of the experiences of medical officers of the Royal British armies and fleets from all parts of the world, which was published in 1863. It describes several times that the administration of quinine and quinine wine is an effective malaria prophylaxis. Of particular interest, perhaps, is a report by W. J. Moore on the Bombay army, entitled  “Treatment of Malarious Fever by the Subcutaneous Injection of Quinine”. ^[50-190] So quinine was not only taken orally, but it was also injected under the skin. The frequent mention and description of quinine suggests that it was not until the 1860s that the efficacy and use of quinine was investigated in more detail. The reports also show that quinine was not always taken or not taken long enough.

1866

In 1866, a work on army hygiene was published in London and Calcutta. In it, the influences of marshes, swamps, banks of tidal rivers etc. are stated: “When an individual person, or a body of troops is temporarily exposed to such influences,they should be highly fed, have coffee in the early morning, use quinine wine, as a prophylactic measure, and have a moderate allowance of spirits issued to them.” ^[52-132]

Also in 1866, the diseases of the navy are reported on: “After dressing, everyone takes 1/2 wine glass full of quinine wine. … Quinine wine (6 – 8 grains in 1 ounce of Marsala wine) was given to the entire crew for 14 days after leaving the rivers. No illness of any kind followed the various expeditions to these notoriously unhealthy regions. …; quinine wine was always administered as soon as one crossed or anchored near the land. It is important that the quinine wine, or the alcaloid itself, is passed on in some suitable form during the middle incubation period (14 days to 3 weeks) after the end of such river or land expeditions. Where this is not done, fever still occurs later.” ^{[9-97] [9-98]}

– “Nach dem Ankleiden nimmt Jeder 1/2 Weinglas voll Chininwein. … Chininwein (6 – 8 Gran in 1 Unze Marsala-Wein) wurde der gesammten Manschaft noch 14 Tage nach Verlassen der Flüsse fortgegeben. Keine Krankheit irgendwelcher Art folgte den verschiedenen Expeditionen in diese notorisch so ungesunden Gegenden. …; es wurde stets Chininwein verabreicht, sobald man in der Nähe des Landes kreuzte oder ankerte. Von Wichtigkeit ist es, dass der Chininwein, resp. das Alcaloid für sich, in irgend passender Form noch während der mittleren Incubationszeit (14 Tage bis 3 Wochen) nach Beendigung solcher Fluss- resp. Landexpeditionen weitergegeben wird. Wo dies unterlassen wird, tritt dennoch später Fieber auf.“ ^{[9-97] [9-98]}

“In San Blas, quinine wine was used prophylactically on landing parties with brilliant success, while those left on board, for whom there was no fear and the remedy was not administered to them, fell ill several times.” ^{[9-200] [9-201]}

– „In San Blas wurde Chininwein bei Landungsmannschaften mit glänzendem Erfolge prophylactisch angewendet, während die am Bord Zurückgebliebenen, für die man keine Befürchtungen hegte und ihnen das Mittel nicht verabreichte, mehrfach erkrankten.“ ^{[9-200] [9-201]}

1867

The following year, 1867, a recipe for quinine wine is published in the drug book “British Pharmacopoeia”:- “VINUM QUINIAE. WINE OF QUINIA. Synonym. – QUININE WINE. Take of Sulphate of Quinia 20 grains, Citric Acid 30 grains, Orange Wine 1 pint. Dissolve, first the citric acid, and then the sulphate of quinia, in the wine; allow the solution to remain for three days in a closed vessel, shaking it occasionally; and afterwards filter. Dose. – 1/2 to 1 fluid ounce.” ^[26-369]

There is also a recipe for quinine tincture: “TINCTURA QUINIAE. TINCTURE OF QUINIA. Take of Sulphate of Quinia 160 grains, Tincture of Orange Peel 1 pint. Dissolve the sulphate of quinia in the tincture with the aid of a gentle heat; then allow the solution to remain for three days in a closed vessel, shaking it occasionally; and afterwards filter. Dose. – 1/2 to 2 fluid drachms.” ^[26-339]

Quinine pills are prepared as follows: “PILULA QUINIAE. PILL OF QUINIA. Take of Sulphate of Quinia 60 grains, Confection of Hips 20 grains. Mix them to a uniform mass. Dose: – 2 to 10 grains.” ^[26-239]

Confection of hips is probably an electurayis, a thickened juice-honey preparation of thick viscous consistency that was used as a medicinal form especially in the medicine of the Middle Ages. ^[25] The recipes of this book also appeared in the following year, 1867, in the Pharmacopoeia of India. ^[24-112]

Also in 1867, Joseph Jones writes about quinine as a prophylactic against malaria fever. At the end of the essay a reference is given to: „ Statistical Report of the Health of the Royal Navy, for the year 1857. Ordered by the House of Commons to be printed , 2 d August , 1859, pp. 78-85.“, ^[17-22] so that we may assume that this is the source for his statements. He writes:

“Under these exposures I have found that Sulphate of Quinia taken in from 3 to 5 grains twice during the day would, in most cases, prevent the occurence of Malarial Fever, and if it failed to ward it off entirely, the attack would be of a very slight character. I have still farther observed that when the climate fever first appeared, with a sense of lassitude, headache and excitement of the pulse, with alternate flushings, it might be arrested by a dose of from five to ten grains of Sulphate of Quinia, in combination with Bicarbonate of Pottassa and Hoffman’s Anodyne. From 5 to 15 grains of the Sulphate of Quinia may be given, according to the urgency of symptoms, united with 15 grains of Bicabonate of Potassa and fʒii of Hoffman’a Anodyne. From 5 to 15 grains of Gum Camphor; the whole to be dissolved in fʒvi of water.” ^[17-9]

“We would recommend the use of Quinia as a preventive of Climate fever, in the following manner: R. Sulphate of Quinia, – grains, iii. Dilute Aromatic Sulphuric Acid, drops, v. Brandy – tablespoonful, 1. Water, – wineglassfuls, ii. Drop the diluted Aromatic Sulphuric Acid upon the Sulphate of Quinia, and then add the brandy and water. Administer twice during the day, after rising in the morning, and just before bed-time.” ^[17-10]

The author then describes various expeditions during which quinine was given. We only quote the passages that also give information about the amounts of quinine given:

“The Bloodhound remained during the entire year on the northern division of the station. In March she steamed about 300 miles up the Benin river; while in the river and for fourteen days afterwards, from three to six grains of the disulphate of Quinine were given to each of the ship’s company as a preventive of fever, and although they were exposed to the emanations from the mangrove swamps for twenty-seven days, only six suffered slightly from fever.” ^[17-15]

“The Bloodhound was employed in January in the River Benin, and during July in the Congo; as long as she remained within these rivers, and for ten days afterwards, four grains of quinine in a quarter of a gill of rum, was administered to every white man on board. One case only resulted from these two expeditions; and in that instance, the person attacked had exposed himself in a most imprudent manner while shooting wild fowl amidst the slimy ooze in the mangrove thickets on the banks of the Benin; whether the patient took quinine as a preventive is not mentioned.” ^[17-20]

“The gig, with one officer and two white men, returned on the 2d, and the other boat on the 5th of December. During their absence they had fine weather, and all returned apparently in good health. Quinine was now substituted for the quinine wine ; four grains were given daily to each person at seven in the morning ; but, notwithstanding this, nine out of the eleven were attacked by remitting fever.” ^[17-21]

We have only quoted texts in the previous section if they contain information about the amount of quinine to be taken. In addition, we have found numerous texts that report on the effectiveness of taking quinine; they are repetitive in their statements and thus offer no added value within the framework of this paper. The interested reader may look them up himself if necessary. They date from the years 1847 ^[34-244], 1854 ^{[39-179] [39-453]}, 1855 ^{[38-10] [38-15] [38-25]}, 1858 ^[16-18], 1860 ^[42-44], 1861 ^{[44-61] [44-308] [46-321]}, 1862 ^[47-37], 1863 ^{[50-146] [50-147] [50-148]}, 1866 ^[52-290], 1867 ^{[17-15] [17-16] [17-17] [17-18] [17-19] [17-20]}, 1871 ^[23-85], 1876 ^{[21-99] [21-100]}.

1869

The English naval reports were also translated into other languages and thus made generally known. The Medical Yearbooks of the kaiserlich-königlichen Gesellschaft der Ärzte in Wien (Imperial and Royal Society of Physicians in Vienna) are a good example. In 1869, Professor Dr Rudolf Ritter v. Vivenot jun. reported in it “On the prophylactic use of quinine against malaria intoxication” – “Ueber die prophylaktische Anwendung des Chinins gegen Malaria-Intoxikation“. ^[8-39]

This work reaffirms that malaria is not only a disease of Africa, but also of Europe. It provides a good overview of the new findings at the time and thus helps us to better understand what was already known about the administration of quinine. We can see not only from this source that the efficacy of cinchona bark and quinine had been known for a long time, but that it was apparently not until the 1850s that it began to be administered regularly and investigated in scientific studies. Therefore, we will quote from this work a little more extensively:

“When a disease appears to be spread over such an extensive area and to be permanently naturalised there, as is the case with the malaria fevers in the country complex of the Austro-Hungarian Monarchy outlined by us at the beginning; – when, as a result of the prevalence of these fevers, the designated stretches of land in the heart of Europe are scarcely inhabited, but, on the other hand, owing to the strategic importance of their position, harbour numerous fortified points (Komorn, Mohacs, Munkics, Peterwardein, Temesvar, Arad, Pola, etc.) whose garrisons are poisoned by the pestilential air of fever and are rendered unfit for service even in peacetime; – when these fevers are so enormously frequent in certain crown lands, e.g. especially in Istria, “that whole regions often appear transformed into hospitals and nearly 1/3 of the total mortality of the country is caused by fever itself or its after-effects” ¹⁾; – when finally they are able to reach such a high level in the only military port of the empire, Pola, that they sometimes represent more than 90% of all illnesses, as appears numerically proven in the excellent work of the Chief Naval Surgeon Dr. A. Jilek ²⁾, representing the entire disease constitution and with a population of 4,000 men, almost 16,000 (exactly 15,828) cases of alternating fever have been recorded within 5 years: so one will have to acknowledge the justification for bringing the question of sanitation in these countries to the fore, and one could hardly remain unconvinced that it deserves to be called a vital question of the places mentioned.” ^{[8-40] [8-41]}

– „Wenn nun eine Krankheit über einen so ausgedehnten Erdstrich verbreitet und daselbst ständig eingebürgert erscheint, wie diess bei den Malariafiebern in dem von uns Eingangs skizzirten Ländercomplexe der österreichisch-ungarischen Monarchie der Fall ist; — wenn in Folge des Vorherrschens jener Fieber die bezeichneten Länderstrecken im Herzen von Europa kaum bewohnt sind, dagegen vermöge der strategischen Wichtigkeit ihrer Lage zahlreiche befestigte Punkte (Komorn, Mohacs, Munkics, Peterwardein, Temesvar, Arad, Pola u. s. w.) beherbergen, deren Garnisonen durch den Pesthauch der Fieberluft vergiftet, schon in Friedenszeit dienstuntauglich gemacht werden; — wenn jene Fieber in gewissen Kronländern, z. B. speciell in Istrien, so enorm häufig sind, „dass ganze Gegenden oft in Spitäler umgewandelt erscheinen und nahe 1/3 der gesammten Sterblichkeit des Landes durch Fieber selbst oder deren Nachkrankheiten bedingt ist“ ¹⁾; — wenn endlich dieselben in dem einzigen Kriegshafen des Reiches, in Pola, einen so hohen Stand zu erreichen vermögen, dass sie, wie diess in der vortrefflichen Arbeit des Obersten Marinearztes Dr. A. Jilek ²⁾ ziffermässig nachgewiesen erscheint, die gesammte Krankheitsconstitution repräsentirend, mitunter mehr als 90% aller Erkrankungen darstellen und bei einem Locostande von 4000 Mann binnen 5 Jahren nahezu 16,000 (genau 15,828) Wechselfiebererkrankungen zu verzeichnen sind: so wird man wohl die Berechtigung anerkennen müssen, die Sanificirungsfrage jener Länder in den Vordergrund zu ziehen, und man durfte sich dabei der Ueberzeugung kaum verschliessen können, dass dieselbe geradezu als eine Lebensfrage der genannten Orte bezeichnet zu werden verdient.“ ^{[8-40] [8-41]}

“A rich collection of concordant facts, attested by numerous and weighty vouchers, the authenticity of which can hardly be doubted, makes the conclusion appear justified that … … our pharmacopoeia, in the prophylactic use of moderate doses of quinine, continued daily over a long period of time, while at the same time observing the other hygienic precautions, offers a remedy which is capable of significantly reducing the susceptibility of the organism to the harmful effects of the ingested malaria toxin.” ^{[8-42] [8-43]}

– „Eine reiche Sammlung übereinstimmender und durch zahlreiche und gewichtige Gewährsmänner beglaubigter Thatsachen, deren Authenticität kaum angezweifelt werden kann, lässt die Schlussfolgerung berechtigt erscheinen, dass … unser Arzneischatz in dem längere Zeit hindurch täglich fortgesetzten prophylaktischen Gebrauch mässiger Gaben von Chinin, unter gleichzeitiger Beobachtung der anderweitigen hygienischen Vorsichtsmassregeln, über ein Mittel gebietet, welches die Empfänglichkeit des Organismus für die nachtheiligen Folgen des aufgenommenen Malariagiftes bedeutend herabzustimmen vermag.“ ^{[8-42] [8-43]}

“By presenting the numerous testimonies in favour of the prophylactic protective power of quinine, which are listed in the relevant literature and which are hardly known in more detail in wider circles (including, in particular, those original reports on the basis of which the British authorities found themselves moved a long time ago [since 1854] to order the regulatory introduction of prophylactic treatment for the troops of the land and sea armies dislocated in fever-ridden areas), it is the purpose of the present papers to ensure that it also receives the attention it deserves from European specialists.” ^{[8-43] [8-44]}

– „Ihr durch Vorlage der zahlreichen, in der einschlägigen Literatur verzeichneten und in weiteren Kreisen wohl kaum ausführlicher bekannten, zu Gunsten der prophylaktischen Schutzkraft des Chinin sprechenden Zeugnisse (darunter namentlich auch jener Original-Berichte, auf deren Grundlage sich die britischen Behörden schon vor einer langen Reihe von Jahren [seit 1854] bewogen fanden, bei den in Fiebergegenden dislocirten Truppen der Land- und Seearmee die reglementarische Einführung der prophylaktischen Behandlung anzuordnen) auch von Seite der europäischen Fachgenossen die gebührende Beachtung zu sichern, ist der Zweck der vorliegenden Blätter.“ ^{[8-43] [8-44]}

A list of the individual reports from France, Great Britain and the United States on the efficacy of quinineaben follows, predominantly beginning in the 1850s. In the following, we quote only those passages that give an indication of the amount of quinine administered.

“In the Medical Reports of the English Navy (No. 15) ¹⁾ [Medcal Times and Gazette. Jan. 1854] Al. Bryson reports in a paper on the prophylactic properties of cinchona bark: “In execution of the 9th article of the instructions given to the physicians of the Royal Navy, the following measures are followed whenever a part of the crew is disembarked in tropical regions in order to fetch water or food or to perform heavy work on land. Before the crew leaves the ship in the morning and after they have returned in the evening, the doctor gives each man 1 drachm of powdered cinchona bark in half a glass of wine. Immediately afterwards, each man receives 1/2 glass of pure wine. When the wine supply is exhausted, it is replaced by a little watered brandy. The healing success of this arrangement can be seen in the following examples:” ^{[8-45] [8-46]}

– „In den Medical-Reports der englischen Marine (Nr. 15) ¹⁾ [Medcal Times and Gazette. Jan. 1854] berichtet Al. Bryson in einer Arbeit über die prophylaktische Eigenschaft der Chinarinde: „In Ausführung des 9. Artikels der den Aerzten der königl. Marine gegebenen Instructionen befolgt man folgende Massregeln, so oft in den tropischen Gegenden ein Theil der Mannschaft ausgeschifft wird, um Wasser oder Lebensmittel zu holen oder am Lande schwere Arbeiten zu verrichten. Ehe die Mannschaft Morgens das Schiff verlässt und nachdem sie Abends dahin zurückgekehrt ist, verabfolgt der Arzt jedem Manne 1 Drachme pulverisirter Chinarinde in einem halben Glase Wein. Unmittelbar darauf erhält Jeder 1/2 Glas reinen Wein. Ist der Weinvorrath zu Ende, so wird derselbe durch etwas gewässerten Branntwein ersetzt. Der heilsame Erfolg dieser Anordnung gibt sich in folgenden Beispielen kund:“ ^{[8-45] [8-46]}

“In his report on the stations of Africa, Bryson ¹⁾ [Alex. Bryson: Report on the climate and principal diseases of the African Station, under the immediate direction of Sir William Burnett] suggested to the Royal Navy to make use of quinine instead of cinchona bark for prophylactic application, and at the same time recommended its use not only during the stay in the unhealthy areas, but also its continuation for at least 14 days after the embarkation of the crew, in order to maintain the protective power of this remedy until after the incubation stage of the disease had passed ²⁾. The proposal was accepted and the results achieved were highly satisfactory. A strong alcoholic solution of amorphous quinine (chinoidine) was mixed into several barrels of wine in the proportion of 25 centigrammes of this salt to 30 grammes of wine (approximately 3 1/2 grains of quinine to 1 ounce of wine). This quinine wine is given to all Africa cruisers. The following excerpts from the reports of the ship’s doctors provide information about the results obtained.” ^[8-46]

– „In seinem Berichte über die Stationen Afrika’s schlug später Bryson ¹⁾ [Alex. Bryson: Report on the climate and principal diseases of the african Station, under the immediate direction of Sir William Burnett] der königlichen Marine vor, sich statt der Chinarinde des Chinin zur prophylaktischen Anwendung zu bedienen, und empfahl gleichzeitig den Gebrauch desselben nicht nur während des Aufenthaltes in den ungesunden Gegenden, sondern auch dessen Fortsetzung noch mindestens 14 Tage nach erfolgter Einschiffung der Mannschaft, um die Schutzkraft dieses Mittels bis nach Ablauf des Incubations-Stadiums der Erkrankung zu erhalten ²⁾. Der Vorschlag wurde angenommen und die erzielten Erfolge waren in hohem Grade zufriedenstellend. Man mischte eine starke alkoholische Lösung von amorphem Chinin (Chinoidin) in mehrere Fässer Wein, in dem Verhältniss von 25 Centigrammen dieses Salzes auf 30 Gramm Wein (annäherungsweise 3 1/2 Gran Chinin auf 1 Unze Wein). Mit diesem Chinawein werden alle Afrika-Kreuzer versehen. Ueber die damit erhaltenen Resultate geben die nachfolgenden Auszüge aus den Berichten der Schiffsärzte Aufschluss.“ ^[8-46]

Detailed reports on the effectiveness of this administration follow. “In another treatise entitled “The endemic fevers of Africa and the prophylactic use of quinine”, derived from the same source, L. J. Hayne, Surgeon of the Royal Navy, expresses himself as follows: … Everyone was given 1 ounce of quinine wine (20 centigrammes = 3 grains of sulphuric quinine per ounce of wine) daily.” ^{[8-47] [8-48]}

– „In einer anderen, „die endemischen Fieber Afrika’s und die prophylaktische Anwendung des Chinin“ betitelten, der gleichen Quelle entlehnten Abhandlung äussert sich L. J. Hayne, Chirurg der königlichen Marine folgendermassen: … Es wurde Jedermann 1 Unze Chininwein (20 Centigrammes = 3 Gran schwefelsauren Chinins auf die Unze Wein) täglich verabfolgt.“ ^{[8-47] [8-48]}

“The ship’s surgeon F. W. Davis, “who has the greatest confidence in the healing power of quinine,” and who took part in the Niger expedition in 1854, as well as in the expedition equipped by Dr. Baikie in 1856, 1857 and 1858, reports ¹⁾ [Statistical Report of the Health of the Navy for the year 1864. 5 Aug. 1867, p. 149 – Blue Book edited by Dr. Alex. E. Makay] that in 1854 he had given the crew of the “Minx” 2 grains of quinine every morning as often as they were busy on the lagoons and along the banks of the Lagos River, and attributes the extremely low mortality rate (with a crew of 47 there were only 2 deaths) to this precautionary measure.” ^[8-48]

– „Der Schiffschirurg F. W. Davis, „welcher das grösste Vertrauen in die Heilkraft des Chinin setzt,“ und sowohl an der Niger-Expedition im Jahre 1854, wie auch an der von Dr. Baikie in den Jahren 1856, 1837 und 1858 ausgerüsteten Expedition Theil genommen hatte, berichtet ¹⁾ [Statistical Report of the Health of the Navy for the year 1864. 5. Aug. 1867, p. 149. — Blaubuch redigirt von Dr. Alex. E. Makay], dass er im Jahre 1854 der Bemannung des „Minx“ so oft dieselbe auf den Lagunen und längs der Ufer des Lagos-Flusses beschäftigt war, jeden Morgen 2 Gran Chinin verabfolgt habe, und schreibt dieser Vorsichtsmassregel die äusserst geringe Sterblichkeit (bei einem Mannschaftsstande von 47 waren nämlich nur 2 Todesfälle zu beklagen) zu.“ ^[8-48]

“On the “Jaseur”, which spent 12 months on the West African coast, only a slight attack of fever was observed despite the ship spending several days in the Cameroon, Brass and Bonny Rivers. The ship’s doctor, Dr. T. D. Allison, attributes this remarkable and gratifying immunity of the crew, apart from the hygienic measures ordered elsewhere, primarily to the prophylactic consumption of quinine. “The same was given” – he reports 2) [Statistical Report of the Health of the Navy for the year 1864. Medical-statistical returns of the West-Coast of Africa-Station. p. 174- 176.]. – to every white person every evening in 4-grain doses dissolved in a little rum, and its use continued for a week after leaving the rivers. I recommended the rum as a vehicle for the quinine, as I found that the crew liked it best in this solution, although in individual cases the first dose of it was vomited out again.” ^[8-49]

– „Auf dem „Jaseur,“ welcher 12 Monate an der westafrikanischen Küste verweilte, wurde trotz mehrtägigem Aufenthalte des Schiffes in den Cameroon-, Brass- und Bonny-Flüssen nur Ein leichter Fieberanfall beobachtet. Schiffsarzt Dr. T. D. Allison schreibt diese bemerkenswerthe und erfreuliche Immunität der Mannschaft, abgesehen von den anderweitig angeordneten hygienischen Massregeln, in erster Linie dem prophylaktischen Genüsse von Chinin zu. „Dasselbe wurde“ — so berichtet er ²⁾ [Statistical Report of the Health of the Navy for the year 1864. Medical-statistical returns of the West-Coast of Africa-Station. p. 174— 176.] — „jedem Weissen allabendlich in 4granigen Gaben, gelöst in etwas Rum, verabfolgt, und dessen Gebrauch noch eine Woche nach dem Verlassen der Flüsse fortgesetzt. Ich empfahl den Rum als Vehikel für das Chinin, da ich in Erfahrung brachte, dass es in dieser Lösung der Mannschaft am besten mundete, obwohl in einzelnen Fällen die erste Gabe davon wieder ausgebrochen wurde.“ ^[8-49]

“In March 1856, the “Bloodhound” went 200 miles up the Benin River and stayed there for 27 days. During the whole time and 14 days later, everyone on board was given 3 – 6 grains of quinine daily. Only 6 men fell ill with malaria as a result of this four-week exposure. … In 1856, this procedure yielded equally favourable or similar results on “Childers”, on which only 9 of 32 men fell ill, most of them slightly, and on “Merlin”, which did not lose a single man to fever during its numerous river expeditions ….. On the latter ship, the entire crew was given quinine wine (6-8 grains in an ounce of Marsala wine) for 14 days after leaving the rivers.” ^[8-50]

– „Im März des Jahres 1856 ging der „Bloodhound“ den Beninfluss 200 Meilen weit hinauf und verweilte 27 Tage in demselben. Während der ganzen Zeit und 14 Tage später noch erhielt Jedermann am Bord täglich 3 — 6 Gran Chinin. Es erkrankten ganz leicht nur 6 Mann in Folge dieser vierwöchentlichen Exponirung an die Malaria. … Gleich günstige oder doch ähnliche Resultate lieferte im Jahre 1856 dies Verfahren auf „Childers”, dem von 32 Mann nur 9, meist leicht, erkrankten, und auf „Merlin”, der bei seinen zahlreichen Flussexpeditionen keinen Mann an Fieber verlor …. Auf letzterem Schiffe wurde der gesammten Mannschaft noch 14 Tage nach dem Verlassen der Flüsse Chininwein (6—8 Gran in eine Unze Marsala-Wein) fortgegeben.“ ^[8-50]

“Also the relevant evidence provided by credible and intelligent travellers, as well as by the English merchant navy, corroborates in every direction the statements made in the reports of the English naval doctors.” ^[8-51] “Thus, among others, the famous traveller to Africa, Du-Chaillu, says: “From the day of my arrival on the coast, I took 3-4 grains of quinine daily in the morning and in the evening, and found it to be an excellent protective agent.”” ^[8-51]

– „Auch die einschlägigen Belege, welche von glaubwürdigen und intelligenten Reisenden, wie auch von Seite der englischen Handelsmarine mitgetheilt werden, bekräftigen nach jeder Richtung die in den Berichten der englischen Marineärzte niedergelegten Aussagen.“ ^[8-51] „So erzählt unter andern der berühmte Africa-Reisende Du-Chaillu: „Von meinem Ankunftstage an der Küste angefangen, habe ich täglich Morgens und Abends 3—4 Gran Chinin zu mir genommen, und darin ein vortreffliches Schutzmittel gefunden.““ ^[8-51]

“When some of our officers, who had not taken the prescribed dose regularly, were attacked by some slight attacks of fever, these always disappeared with suitable treatment after the administration of quinine, increasing to 10 grains per dosi. With the disappearance of the symptoms I returned to the original dosage … .” ^[8-52]

– „Wenn einige unserer Officiere, welche die vorgeschriebene Dosis nicht regelmässig eingenommen hatten, von einigen leichten Fieberanfällen befallen wurden, wichen dieselben bei geeigneter Behandlung stets nach Verabreichung von Chinin, steigernd bis auf 10 Gran pro dosi. Mit dem Schwinden der Symptome kehrte ich zur ursprünglichen Gabengrösse zurück … .“ ^[8-52]

“The proven precautionary principle which reliably protects against disease consists, according to a communication from my dear friend Dr. G. y. Liebig, based on his own experience and several years’ stay in the East Indies, in taking 10 grains of sulphuric quinine either in the morning before entering that unhealthy region or daily for as long as one stays in Terrai.” ^[8-53]

– „Die bewährte Vorsichtsmassregel, welche sicher gegen Erkrankung schützt, besteht laut einer auf eigene Erfahrung und mehrjährigen Aufenthalt in Ostindien gestützten Mittheilung meines geehrten Freundes Dr. G. y. Liebig, in einer Gabe von 10 Gran schwefelsaurem Chinin, die entweder Morgens vor dem Betreten jener ungesunden Gegend, oder täglich so lange man in Terrai weilt, zu sich genommen wird.“ ^[8-53]

“According to a communication from Dr. Hainmond, the facts laid down in Van-Buren’s memorandum on the prophylactic properties of quinine have been fully confirmed by the experience gathered since then by the United States Military Medical Department; the sulphuric acid cinchonine has also been used in doses of 5 to 8 grains with no less favourable results, a preparation which, in comparison to the much more expensive sulphuric acid quinine, deserves warm recommendation from an economic point of view.” ^[8-59]

– „Einer Mittbeilung Dr. Hainmond’s zufolge wurden die in Van-Buren’s Denkschrift niedergelegten Thatsachen über die prophylaktischen Eigenschaften des Chinin durch die seither von dem Militär-Sanitätsdepartement der Vereinigten Staaten gesammelten Erfahrungen vollinhaltlich bestätigt gefunden; auch sei das schwefelsaure Cinchonin in Gaben von 5 bis 8 Gran mit nicht minder günstigen Erfolgen in Anwendung gezogen worden, ein Präparat, welches im Vergleich zu dem ungleich kostspieligeren schwefelsauren Chinin, aus ökonomischen Rücksichten warme Anempfehlung verdiene.“ ^[8-59]

It is quoted from a letter “from the then Chief Surgeon of the English Army, Director General A. Smith, to the Inspector General of the English Military Hospitals in the Crimea” ^[8-59] dated 27 July 1855: “Since I am now in a position to have a sufficient quantity of this remedy at my disposal to be able to supply each of the 35,000 men of our army with 5 grains (= 36 centigrammes) of it every day, 1) I ask you to take such measures as you deem suitable to induce the doctors of the army to administer this remedy, in the hope of preventing the outbreak of fever.” ^{[8-59] [8-60]}

– “von des damaligen Obersten Chefarzt der englischen Armee, dem General-Director A. Smith, an den General-Inspector der englischen Militärspitäler in der Krim” ^[8-59] … “Indem ich demgemäss heute in der Lage bin, über eine genügende Menge dieses Mittels zu verfügen, um jeden der 35,000 Mann unseres Heeres täglich mit 5 Gran (= 36 Centigrammes) davon versorgen zu können, ¹⁾ so ersuche ich Sie, die Ihnen geeignet dünkenden Massregeln ergreifen zn wollen, um die Aerzte der Armee zur Verabreichung dieses Mittels zu veranlassen, in der Hoffnung den Ausbruch der Fieber dadurch hintanzuhalten.” ^{[8-59] [8-60]}

It is suggested to carry out experiments oneself. In this context, the author proposes to carry out a trial in Pola “to test the prophylactic efficacy of this remedy on individuals who are not yet infested and still completely free of fever. During the whole period of the experiment, each man would be given a daily dose of 3 grains of sulphuric quinine, preferably dissolved in an ounce (4 tablespoons) of wine, rum or brandy (as quinine wine or quinine liqueur). The mixture could already be prepared in Vienna under official control in the appropriate quantity, sent from there in barrels to the place of the experiment and handed over to the military doctor or officer responsible for the punctual and conscientious execution of the experiment for safekeeping.” ^[8-62]

–  „um die prophylaktische Wirksamkeit dieses Mittels auf noch nicht durchseuchte, noch vollkommen fieberfreie Individuen zu prüfen. Während der ganzen Versuchszeit wäre jedem Mann täglich eine Gabe von 3 Gran schwefelsaurem Chinin zu verabfolgen, und zwar am besten gelöst in einer Unze (4 Esslöffel) Wein, Rum oder Branntwein (als Chininwein oder Chininliqueur). Die Mischung könnte bereits in Wien unter amtlicher Controle in entsprechender Quantität vorräthig bereitet, von da in Fässchen nach dem Versuchsorte versendet und dem für die pünktliche und gewissenhafte Ausführung des Versuches verantwortlichen Militärarzt oder Offizier in Verwahrung übergeben werden.“ ^[8-62]

“Once the prophylactic power of the daily dose of 3 grains standardised for the first series of experiments has been sufficiently established, it can subsequently be reduced to 2 and even 1 grain in order to learn the minimum limit of prophylactic efficacy by experimental means and to enable the possible achievement of a cost reduction by 1/3 – 2/3. It will then also be the subject of later series of experiments to find cheaper quinine substitutes than: Cinchonin, Salicin, or the sulphites (sulphurous acid magnesia) recommended by Polli, or the barks of Cornus florida and Prunus virginiana, which according to Van Buren are often used in America as proven fever remedies, to test their prophylactic protective power.” ^[8-63]

– „Ist einmal die prophylaktische Kraft der für die erste Versuchsreihe normirten Tagesgabe von 3 Gran genügend sicher gestellt, so kann dieselbe in der Folge auf 2 und selbst 1 Gran herabgesetzt werden, um auf experimentellem Wege die Minimalgrenze der prophylaktischen Wirksamkeit kennen zu lernen, und die eventuelle Erzielung einer Kostenreduction um 1/3 — 2/3 zu ermöglichen. Auch wird es dann Gegenstand späterer Versuchsreihen sein, billiger im Preise stehende Chininsurrogate als: Cinchonin, Salicin, oder die von Polli empfohlenen Sulfite (schwefligsaure Magnesia), oder die laut Van Buren in Amerika als bewährte Fiebermittel vielfach in Anwendung gezogenen Rinden von Cornus florida und Prunus virginiana auf ihre prophylaktische Schutzkraft zu erproben.“ ^[8-63]

An postscript was added at the end of the paper: “Postscript. The late publication of this memorandum, which was already ready for printing in April, not only allowed us to enrich it with some valuable documents that have come to our knowledge since then, but it also puts us in the pleasant position of being able to add the supplementary information that the High Imperial War Ministry immediately ordered that the measure we had suggested and proposed be carried out on a larger scale as early as this summer.” ^{[8-64] [8-65]} It is reported “that the Navy Section of the War Ministry immediately granted permission to carry out an experiment with the prophylactic administration of quinine in Pola under the modalities outlined above. For the time being, 500 men are being used for this experiment, and since the month of May they have been administered 3 grains of sulphuric quinine a day, dissolved in 1/16th of a teaspoon of a Seitel of rum ¹⁾under the name of “stomach liqueur”. At the same time as the above order, the High Imperial War Ministry has decreed that the garrisons of the fortresses of Komorn and Peterwardein should also be subjected to the prophylactic treatment on an experimental basis. In Komorn, 1/32 Seitel of “Magentinctur” prepared in Vienna (prepared from 40 Maas of rectified spirit of wine [0.914] to 21 ounces and 8 scruples of sulphuric acid quinine) is administered per head daily, while in Peterwardein Extractum Nucis Vomicae is used instead of quinine for the trial. … ¹⁾ 1/16 of a Seitel = about 1/2 ounce or 2 tablespoons. This quantity of the vehicle was found to be necessary to keep the quinine dissolved in it. With a reduction in the amount of quinine, the amount of rum can also be reduced.” ^[8-64][8-65]

– „Nachschrift. Die verspätete Drucklegung dieser schon im Monate April druckfertig vorgelegten Denkschrift gestattete uns nicht nur dieselbe noch mit einigen uns seither zur Kenntniss gekommenen werthvollen Belegen zu bereichern, sondern sie versetzt uns in die angenehme Lage, derselben die ergänzende Mittheilung hinzuzufügen, dass von Seite des hohen Reichskriegsministeriums sofort die Anordnung getroffen wurde, um die von uns angeregte und in Vorschlag gebrachte Massregel bereits im laufenden Sommer u. zw. in grösserem Massstabe versuchsweise zur Ausführung zu bringen.“ ^{[8-64] [8-65]} Man berichtet, „dass von Seite der Marinesection des Kriegsministeriums sofort die Bewilligung ertheilt wurde, zunächst in Pola einen Versuch mit der prophylaktischen Verabreichung des Chinin unter den oben skizzirten Modalitäten auszuführen. Es werden daselbst zu diesem Experimente vorläufig 500 Mann verwendet, welchen, schon seit Monat Mai, täglich je 3 Gran schwefelsauren Chinins, gelöst in einem 1/16 Seitel Rum ¹⁾ unter der Bezeichnung „Magenliqueur” verabfolgt wird. Gleichzeitig mit obiger Anordnung wurde von Seite des hohen Reichs-Kriegsministeriums die Verfügung getroffen, auch die Garnisonen der Festungen Komorn und Peterwardein versuchsweise der prophylaktischen Behandlung zu unterziehen; u. zw. wird in Komorn 1/32 Seitel in Wien bereiteter „Magentinctur” (bereitet aus 40 Mass rectificirtem Weingeist [0.914] auf 21 Unzen und 8 Scrupel schwefelsauren Chinins) per Kopf täglich verabfolgt, in Peterwardein dagegen Extractum Nucis Vomicae statt des Chinin zum Versuche verwendet. … ¹⁾ 1/16 Seitel = etwa 1/2 Unze oder 2 Esslöffel. Diese Quantität des Vehikels wurde als die erforderliche ermittelt, um darin das Chinin gelöst zu halten. Mit Verminderung der Chiningabe kann auch jene der Rumportion eine Verminderung erfahren.“ ^{[8-64] [8-65]}

1874

A book on tropical diseases published in 1874 states: “I should strongly recommend that persons who reside in malarious districts, or who in any way are exposed to the influ+ence of malaria, should now and then take the sulphate of quinine, as it serves as a preventive; or should the person be attacked, he would have a milder and more manageable disease than another who has not been so protected. The best mode of giving quinine for such a purpose is in the form of quinine wine; four grains to every ounce of sherry; of which, especially during the fever season, one ounce should be taken every morning before going out, and repeated if required in the afternoon.“ ^[22-55]

1883

The Handbook of Cinchona Culture, published in 1883, states about the cinchona bark:- „A large amount of the produce serves for the preparation of quinine wine; great quantities also, in British India especially, are intended for the manufacture of Quinetum, which possesses all the Cinchona alkaloids in one, thus named and highly recommended by Dr. de Vrij.“ ^[20-212]

The general catalogue of the army and navy stores, published in 1883, offers aërated quinine for sale, Quinine and Tonic, ^[19-31]

quinine pills, quinine wine and quinine syrup. ^[19-589] In the context of the military, this is the oldest reference to a sparkling quinine drink that we have been able to find.

Wine or spirits as solvent?

It is noticeable that in the sources we found, quinine was regularly dissolved in wine. Rarely is there talk of using a distillate such as rum, brandy or gin. This corresponds to the instructions of the doctors of the Royal British Navy not to switch to brandy until the wine supply had been used up. ^[8-46]

A letter to the editor from the year 1800 also confirms this fact. In The Naval Chronicle it is written: “Mr. Editor, It was originally the custom to serve seamen with their allowance of spirits undiluted: the method, now in use, of adding water to it, was first introduced by Admiral Vernon in 1740, and obtained the appellation of Grog. This was a great improvement; for the quantity of half a pint, which is the daily legal allowance to each man, will intoxicate most people to a considerable degree, if taken at once in a pure state. The superiority of wine over spirits in any shape was so conspicuous, that towards the end of the war, the Fleets in the West Indies and North America were supplied with nothing but wine, and with a success sufficient to encourage the continuance of the same practice in future.” ^[1-53]

Chinin in Cocktails

Quinine was not only put into wine and spirits, but it was also something that was consumed in cocktails. Robert Tomes writes in his book “Panama in 1855” that people there not only took quinine pills, but also often drank cocktails in which the bitter substances were replaced by quinine: “I say nothing by way of protest against the frequent practice of drinking quinine cock-tails in which quinine is substituted for bitters and the by no means agreeable but constant habit of freely indulging in quinine pills; for these are excusable, if not necessary on the score of health. It is a melancholy fact that such is the unhealthiness of Aspinwall [Colón] that its inhabitants are obliged to mix medicine with their daily drink, and to pass around their pill-boxes with the frequency of a French snuff taker of the ancient régime. I have been seriousliy invited, time and again, to drink quinine cocktail and to help myself out of a proffered box, to a pill or two, which, I need not say, I politely declined.” ^{[2-94] [13-63]}

Also interesting in this context is a recipe in Jerry Thomas’ book from 1862. In the appendix, the “Manual for the Manufacture of Cordials, Liquors, Fancy Syrups, &c. &c.”, written by Professor Christian Schulz, there is a recipe for “Fever Drops”. For these, among other drugs, cinchona bark, called Peruvian Bark in the recipe, is dissolved or macerated in alcohol. The instruction is to take three to four teaspoons of it daily. ^{[2-98] [14-160]}

Summary

Even though the malaria-preventing effect of quinine had been known for a long time, it was apparently not until the 1850s that quinine was studied in detail; it was administered mainly as quinine wine in accordance with the official recommendation. As a rule, it was only dissolved in other spirits when wine was no longer available. Also, it was still being tested and clinical trials had not yet been completed. These were still started at the end of the 1860s.

It is also noticeable that tonic water is never mentioned in connection with malaria prophylaxis or treatment.

In the next part of this series, we analyse the traditional recipes for quinine wine. We answer the question of how much quinine was contained in the wine, whether it really helped, and how in relation to this the quinine wines available today are to be understood.

Sources

1. https://archive.org/details/navalchronicleco03lond/page/52/mode/2up/search/grog Anonymus: The Naval Chronicle. Vol. 3. London, 1800.
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14. Christian Schulz, in: Jerry Thomas: The Bartenders‘ Guide, A Complete Cyclopædia of Plain and Fancy Drinks, Containing Clear and Reliable Directions for Mixing All the Beverages Used in the United States, Together with the Most Popular British, French, German, Italian, Russian, and Spanish Recipes, Embracing Punches, Juleps, Cobblers, Etc., Etc., Etc., in Endless Variety. To Which is Appended a Manual For The Manufacture of Cordials, Liquors, Fancy Syrups, Etc., Etc., After the Most Approved Methods Now Used in the Destillation of Liquors and Beverages, Designed For the Special Use of Manufacturers and Dealers in Wines and Spirits, Grocers, Tavern-Keepers, and Private Families, the Same Being Adapted to the Tteade of The United States and Canadas. The Whole Containing Over 600 Valuable Recipes by Christian Schultz. New York, Dick & Fitzgerald, 1862.
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explicit capitulum
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