by Eric Flint
Probenicid is an organic acid that competes with the penicillin class and other drugs for excretion through the kidneys. This competition for excretion increases both the level and the time duration of the penicillin class drugs in the blood stream. A substituted benzoic acid derivative, probenicid should be easy for various pharmaceutical manufacturers to make as soon as the coal tar recovery system is on line. It will be vital in extending the effectiveness of penicillin when it first comes on line.
Chloramphenicol is available in small amounts in canon as of 1633, and the formula and manufacturing information was passed on to the King in the Low Countries at that time. (Grantville Gazette II) Thiamphenicol has been advocated for use in the 1632 universe by some, but here in the US, this drug is limited to veterinary use. Research shows that thiamphenicol has been used overseas (particularly in Brazil) in humans for the treatment of Donavanosis and chancroid. That same research does show that there appears to be no evidence of aplastic anemia associated with thiamphenicol, but the absolute numbers of treated patients published is not enough to consider it safer. There is some question as to the relative effectiveness compared to the chloro form. The big questions then become, "what is the chance that there were veterinary stocks in Grantville at the time of the Ring of Fire?" and "Would someone recognize that it might be easier to make than the chloro form?'
Sulfas of various sorts are being produced in fair quantities by early 1633.
Metronidazole is another drug that will vastly improve the treatment of many diseases, not just STIs. Deceptively simple, it probably won't be available until the end of the 1630s. The antifungal azoles are more complex, related compounds, and will probably be available in early 1640.
Other antibiotic medications (the tetracycline group, the erythromycin group, the aminoglycosides, and the derivatives of penicillin known as cephalosporins) will probably have to wait for assorted American (both North and South), Polish, Ukrainian and Russian soil samples, and the further development of tech levels in the late 1640 and into the 1650 time frame. Iver also pointed out that most of them were serendipitous discoveries from various mold specimens, so the various fungal derived antibiotics may not be exactly reproduced compared to the structures known today.
Ultimately, the "venereal diseases" (sexually transmitted infections) are controllable with a combination of careful population surveillance, by prenuptial, prenatal and blood bank testing; breaking the chain of infection by treating both the index case and all intimate partners (where possible); and good hygiene with plenty of soap and clean water. Ultimately, quarantine for patients who are both chronically infected and unable or unwilling to avoid intimate contact with others must be considered. Treatments available will improve over the span of several years, as the knowledge of how to make chloramphenicol, penicillins and sulfa drugs start to spread across the continent.
References
Online medical dictionary: http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=
Online medical encyclopedia: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
Cooper, Iver: Industrial Alchemy, Parts III and IV, pending publication
"Venus and Mercury" Grantville Gazette, Volume 24
http://www.cdc.gov/std/treatment/2006/rr5511.pdf (This is the current version, however I have filtered the recommendations based on what would be available in the 1998-2000 edition, adapted to the 1630's tech base.)
Control of Communicable Diseases in Man, 14th edition 1985 US CDC
http://en.wikipedia.org/wiki/Sexually_Transmitted_Infection
http://www2a.cdc.gov/stdtraining/Self-Study/ (requires registration and professional status, sorry)
http://www.cdc.gov/STD/training/
The Travel and Tropical Medicine Manual, Second Edition, Section V, Jong & McMullen, Saunders 1995
Davis, BD; Dulbecco, R; et al, Microbiology, 2nd ed Harper and Row, 1973 (a common microbiology text book for laboratory, pre medical and advanced nursing students in the mid 1970s)
The Merck Manual of Diagnosis and Therapeutics, 17th Ed, Merck Research Laboratories, 1999 (centennial edition)
Merck's Manual of Materia Medica, Merck & Co, 1899
Common Childhood Diseases in the 1630s, Part One: Fevers with Rashes
by Gus Kritikos
One of the greatest limitations on population growth in the 1630s (both OTL and NTL), and in the Third World today, is the number of children who die before their tenth birthday. The emotional and physical toll on the parents (especially the mothers) was literally incalculable, and was part of the reason used to "justify" treating women as the "weaker sex."
A surprising number of these deaths are preventable with up-time technology that is easily adapted to down-time situations. This includes improved food and water sanitation; improved food sources and nutrition; appropriate waste disposal; and appropriate immunizations, which may be active (relatively easy), or passive (which requires a bit higher technology). Some of the diseases, including smallpox and polio, have no known reservoirs outside of man, and might be eventually eliminated in the NTL.
Additionally, the down-time authorities have experience in limitations of travel, the use of isolation wards (lazarettes) and traveler quarantines as a method of reducing the spread of disease. Information on the germ theory, Koch's postulates and up-time hygiene will put these methods on a rational basis, and improve the effectiveness of the techniques. This improvement alone will limit the spread of many of the pestilences "scheduled" to appear between 1634 and 1700. This is the main reason why Mike Stearns, James Nichols, Beulah McDonald and Mary Pat Flanagan are determined to spread this information as widely as possible.
In April 1634, Anna Krause did a report on childhood diseases in the area around Grantville. She received a blue ribbon for her efforts, and was pushed toward a career in nursing/medicine by Hennie DeVries, RN. Fraulein Krause is the first known down-timer to study what we know now as Epidemiology.
Rashes with Fevers
Down-time physicians would not have been able to differentiate many of these diseases before the arrival of up-time information. The "Six Diseases" were finally separated in the late 1800s, and named as such in the early 1900s. All of them start with fevers and muscle aches, loss of appetite, nausea, and sometimes diarrhea. Often sore throats and headaches are common with all of these infections.
Bacterial
Scarlet Fever/Scarletina, known as the Second Disease, as it was the second rash described as a separate entity. Normally associated with a high fever (103 F is common, and 105 F is not unusual), and a bright red rash that may be patchy, all over the body or just confined to the tongue (the so called "Strawberry Tongue"). The rash on the body is peculiar, in that it feels as rough as sand paper. This is the only rash in this group that is not caused by a virus, but by toxins produced by Streptococcal throat infections. The tonsils at the back of the throat are usually swollen and covered with pus. Lymph nodes in the neck, usually along the front side, are swollen and tender. Without antibiotic treatment, these throat infections will eventually lead to many problems with the heart, kidneys, ears or lungs.
Viral Flat Rashes
Measles
The Arab Physician/Philosopher Abu Bakr Muhammad ibn Zakariya Razi, better known in Europe by his Latinized name, Rhazes, first described measles (First Disease) as compared to smallpox in the 9th Century (CE). Despite this, there was enough overlap between measles and other viral rashes to prevent clear delineation for another 900 years. The "three C's" (cough, coryza (runny nose and sore throat) and conjunctivitis) are some of the initial symptoms, but these are also common to influenza. Koplick's spots, blue white dots on red rings inside the mouth are present from about 24 hours before the rash starts to 48 hours afterwards, and are diagnostic for the measles. Two to four days after the onset of the fever, a flat red rash spreads from hairline down the body, turning from red to brown over the course of several days, and resolves in the same head-to-toe pattern, commo
nly with dandruff-like flaking of the skin as the rash resolves. The rash is typically most prominent along the shoulders, back of the neck and upper arms, but the rest of the body, including the palms and soles, may be involved. The dandruff-like flaking skin will not extend to the palms and soles.
The virus can be transmitted from person to person starting with the first appearance of the "three C's" (up to 5 days before the rash is noticeable) and extending for around five days after the rash appears. As the disease is highly infectious, upwards of 90% of non-immune people will catch the infection from even brief contact with an active case. Major complications of measles infections include ulcers of the delicate membranes of the eye, which can lead to scarring and blindness, and weakening the body's immune system for some time after the infection, making a secondary, bacterial, infection more likely. These infections often include severe ear infections that may lead to deafness and pneumonia, which can be fatal. Other problems which can occur include an aseptic meningitis (a cause of seizures), viral pneumonitis (which again sets the stage for pneumonia) and even an inflammation of the liver. A significant diarrhea may also occur. Malnourished children, especially those suffering from Vitamin A deficiency, are ten times as likely to die from the infection.
Care is almost completely supportive, even in OTL. There are some antiviral agents which help shorten the period of illness, but they are rarely used. Fever control, oral hydration, and relief of the itching as the rash starts to resolve will be the main treatment for simple cases. Cases that are more complex will require intravenous fluids for severe dehydration, possibly antibiotic treatment for the secondary infections, or medications to control seizures associated with the high fever or from the inflammation of the tissues surrounding the brain (meningitis). Based on Iver Cooper's chemical time lines, I believe that the drug paraldehyde will be the first available medication to control acute seizures some time in 1633 or early 1634, as it is a cyclic form of formaldehyde. Barbiturates are more complex, having a substituted ring structure (2 nitrogen and four carbon atoms, but they will most likely be the second group of drugs in this classification, as they were in OTL, as they are much simpler than the other drugs. Vitamin A supplementation alone has been shown to reduce the risk of death by 50% even in the face of significant protein calorie malnutrition or young age. High dose carrot juice will probably be among the safest ways to deliver the vitamin in the 1630s, as the vitamin itself is potentially toxic.
Prevention will be a matter of case tracking and isolation of contacts, until the development of virus culturing techniques capable of producing live virus vaccines, probably in the late 1640s or early 1650s.
Koplick's spots (small blue white dots on inside of cheek) (photo courtesy of the WHO website)
Rubella, also known as "German" or "Three Day Measles," was the Third Disease to be differentiated by physicians in OTL. Generally milder, up to one half of all the patients may be almost without symptoms. The fever is generally lower, the rash is very mild, and the amount of discomfort is lower with the "Three C's" being almost absent in many cases. The great tragedies occur when a young woman in the first months of her pregnancy contracts the disease. This prenatal rubella exposure results in marked congenital growth and mental retardation, hearing loss, heart disease, and eye problems. An interesting point that will make an excellent story line is that some cases of congenital rubella may remain infectious until the child's first birthday.
Treatment is again supportive, with oral hydration and fever control. The rash is generally not as "itchy" as that of true measles.
Prevention again consists of case tracking and contact isolation. With rubella, there will be the development of "rubella parties," where nubile young females who are not known to have had the disease will be exposed to a known case of rubella and isolated together for several days. This will be the best method of preventing the complications of congenital rubella until the development of advanced live virus vaccines.
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The term "Fourth Disease" is no longer recognized, as it was actually several different, similar rashes, all of which were mild and require no further discussion here.
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Erythema Infectiosum
The Fifth Disease to be isolated is characterized by a high fever, malaise and a loss of appetite for two or three days, followed by the development of the classic "slapped cheek" rash, a solid, bright red rash limited to the cheeks. A peculiar, more generalized rash will often develop over the body in the following days, which has been described as looking like a fishing net dipped in red paint was applied to the body. Usually a mild disease, limited to children under age six, it requires only supportive care. Barring problems from the high fever (which is controllable), there are no long-term problems.
Roseola infantum
The Sixth Disease is another disease of early childhood, usually occurring before the second birthday. Again, it is characterized by a high fever (up to 104F/40C), the possibility of seizures associated with the fever, and followed by a rash on the body a day or so after the fever subsides. This is a more generalized rash than that of Fifth Disease, and again, does not cause problems with itching.
Viral pustular rashes:
Small Pox is well known to down-time physicians, who have survived and then treated waves of this disease for their entire lives. The infection starts with a fever with prostration, headaches or backaches several days before the rash appears. The rash starts in the mouth (enanthem) and then spreads to the face around the mouth and nose after a day or so. Over the next several days, the rash spreads to the extremities especially the distal limbs, including the palms and soles, but rarely affects the trunk or abdomen. There is only one crop of lesions, which initially appear dimpled, but later extend deep into the skin, resulting in healing with scarring in survivors. Saliva, fluid from the skin lesions and scabs are very infectious. Fatality rates in naïve populations were up to 30%, with younger children and infants being more likely to die. Some varieties, including flat and hemorrhagic forms, have higher (90+%) fatality rates. Survivors will have life long immunity to the disease.
Chicken Pox, on the other hand, is a milder disease with a much lower fever, much less prostration and a more variable course. Patients will show multiple crops of lesions, which are superficial ("dew on rose petal"), and which are more on the body than the face and limbs, and very rarely on the palms and soles. These pox usually heal without scarring because of the more superficial nature of the infection. Fatalities are uncommon, but possible when the disease is contracted by older persons who were not exposed as children, as lung infections may result. The name "chicken pox" is not related to an infection of fowl, but from the idea that the disease was a weaker, or "chicken," form of small pox.
Both diseases are highly infectious by airborne spread from early in the disease, and teens or adults who are exposed to the infection but do not get the infection have probably been exposed as young children even if no history (or typical scarring) is present.
Rickettsial infections
There are several infections in this classification, including Typhus and the various Spotted Fevers. None of them are directly transmissible from person to person, instead being passed by an arthropod vector, usually body lice or ticks. The problems with Typhus are already in canon in several stories, and the spotted fevers will be discussed in another article.
Making the Diagnosis Clinically
These diseases are mostly easy to diagnose once they are in the acute stage, as each one has a consistent pattern. The trick is to make the diagnosis early enough to help quarantine patients to prevent the spread of the disease. All of the diseases tend to follow several stages of infection:
Asymptomatic or Latent stage: these infections usually take between 5 and 20 days from exposure to the first symptoms, which usually consist of fever, aches, pains and general discomfort.
Prodrome stage: starting with the first, usually non-specific symptoms noted above, the patie
nt is now infectious. Generalized discomfort quickly progresses, with nausea, vomiting or diarrhea and loss of appetite and energy commonly occurring.
Active infection stage: This is usually where the characteristic rashes start to become obvious. With the notable exceptions of small pox and chicken pox (which remain infectious until the last of the scabs are gone), most of these diseases are infectious for only a few days after the rash becomes apparent. Very young, malnourished or otherwise debilitated children can become frighteningly ill in a very short time at this point, mostly due to dehydration associated with the fevers and diarrhea. Care consists of reducing the fevers, maintaining hydration and nutrition, and preventing secondary infections (most often pneumonia) by encouraging deep breathing and coughing to prevent excessive mucus from clogging the airways. Antibiotics will help with the secondary infections if they are caught in time.
Resolution stage: The patient is no longer miserable from a fever, the rash is starting to resolve, and the appetite is coming back. As previously noted, small pox and chicken pox are both still infectious at this time, until the "pox" are fully resolved. The other infections are no longer infectious after the fever drops and the rash starts to resolve.
Brain Fevers
Meningitis is an inflammation of the membranes that cover the brain. There are two basic types: "aseptic" (because nothing grows when the spinal fluid is cultured), caused by one of several viri, which is usually mild, or "purulent," (caused by bacteria or fungi) which is more often severe, and may result in disability or death. Both the bacterial and fungal types may result from the spread of an infection from an infection of the sinuses, blood, facial skin or scalp. An interesting point is that "encapsulated" organisms such as pneumococcus and meningiococcus, or fungi such as Cryptococcus cause many cases of purulent meningitis. These capsules contain sugar groups that generally act to protect the bacteria from attack by the body's defenses. These same sugar groups can be processed (when the technology is available) into vaccines to provide significant protection from these infections.