Essay on Typhoid Fever

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Many people think of typhoid fever as something that only occurred in the past, but the truth is that typhoid fever is a popular cause of death in the developing world. This sample essay, one of the many features offered by Ultius, illustrates how in areas where poverty and underdevelopment are high, typhoid fever is a dangerous killer that is responsible for some 200,000 deaths every year. 

Typhoid: Still a Killer

According to the World Health Organization (WHO):

• In 1984 there were approximately 16 million cases of Typhoid fever resulting in almost 600,000 deaths
• In 2000 there were approximately 22 million cases of Typhoid fever resulting in approximately 200,000 deaths

With the rising threat of the Zika virus, greater attention has been directed toward diseases that were once thought to be controlled. Typhoid fever results in approximately 16-33 million cases and 200,000 to 600,000 deaths annually, worldwide, although concentrated mostly in developing and underdeveloped areas such as: 

• Africa
• India
• Bangladesh
• Papua New Guinea
• Indonesia
• Pakistan

In developed countries, Typhoid is not a disease commonly feared, or even discussed much unless someone is traveling abroad. It is only then that it becomes an issue, perhaps even a surprise issue. If travelling abroad, you might need to get a shot.

The solution is education, sanitation and vaccination

In some developing and undeveloped countries, such as Somalia where clean water and sanitation is wanting, and extreme poverty persists, Typhoid fever remains a major health risk and killer. Treatment of typhoid fever with antibiotics has been preferred after early results with some vaccines were less than optimal, but as is often the case, the bacteria responsible for Typhoid fever developed resistance. Some researchers and the World Health Organization (WHO) have suggested it is time to put it back on the United Nation’s front burner and focus again on vaccines that can do more to eradicate this dangerous disease in the developing and undeveloped world. But education and infrastructure are just as important to eradication of Typhoid fever.

Definition of typhoid fever

What is commonly known as Typhoid fever (not to be confused with Typhus, a different disease) is the result of infection with Salmonella enterica serovar Typhi (also called S. typhi), waterborne gram negative aerobes, and pathogens which affect only humans. As a consequence of antibiotic regimens in some undeveloped and developing countries, several strains of Typhoid have developed, such as:

• Paratyphoid strain A
• Paratyphoid strain B
• Paratyphoid strain C
• MDR (multi-drug resistant) strains which can pose additional risks

Historically, while an ancient disease (some estimates say 15,000–150,000 years), it was not until the mid-19th century that it began to be understood, and distinguished from Malaria and Typhoid fever. Sir William Osler provided the paradigmatic clinical description. Given the nature of transmission of Typhoid fever, it was generally seen during military conflicts, and in fact there were more fatalities from Typhoid fever during the American Civil war than combat deaths. Once the epidemiology of Typhoid fever was understood, its effects were minimized in developed countries through sanitation and education. 

Risk factors of typhoid fever

Typhoid fever, infection by the S. typhi bacteria remains one of the most prolific threats in some developing and undeveloped countries. Once the mechanism of Typhoid fever was understood, that is “the fecal-oral route by means of contaminated water or food,” its effects were minimized in developed countries through improvements in water and sanitation facilities and systems, and education, in particular in urban centers, with indoor plumbing and sewer systems. In rural areas and in slums and poverty stricken areas all over the undeveloped and developing world, there continues to be little hope for these types of improvements in areas without political clout or the wherewithal to make changes to their own infrastructure without substantial outside help. Moreover, education about sanitation and water usage habits and personal hygiene remain problematic in these areas as well. Consequently, the risks in rural areas and poor urban centers remain quite high. In addition, since the disease persists in places which are the least developed on earth, keeping track of the disease, and researching its statistical elements has been difficult, and has generally required some form of extrapolation to give estimates of worldwide or even countrywide incidence of the disease where it is prevalent.

Typhoid epidemiology

In his 2001 study on Typhoid fever epidemiology, Prof. Bir Singh of the Centre for Community Medicine in New Delhi, listed some factors. As for the affected age group, Singh reported that:

• Although the disease can occur at any age, it generally affects children and young adults
• It is most prevalent among 8-13-year-olds
• In the slums of Delhi, the disease was shown to affect children aged 1-5 years old as well

This fits with the conclusion by DeRoeck, et al., that because the prevalent group affected by Typhoid fever is school age children, and not in the 1-5-year-old range, policymakers, aid organizations and the U.N. had lost interest in the disease as 8-13-year-olds is not as favored a group as the latter younger children.

“…whereas policymakers have prioritized vaccines that reduce the rates of illness and death among children under 5 years of age, typhoid fever has long been considered a disease of school-aged children.”

Socioeconomic factors

Singh also notes that Typhoid fever is a disease that primarily attacks the poor, given its association with lack of sanitation and safe water supply, but others have noted that Typhoid fever can attack any traveler if they travel to those areas that are at risk, and fail to follow safe sanitary procedures or take adequate preparations with inoculation. Singh also notes that some questions have arisen regarding whether malnutrition enhances susceptibility to the disease by

“altering the intestinal flora or other host defences.”

He goes on to report that the incubation period of the disease is usually 10-14 days, but can be as short as 3 or as long as 21 days, depending on the extent of infection.

Transmission of typhoid fever

For those intimately familiar with the conditions under which this disease manifests, where open toilets predominate, where rivers serve as water sources, toilets, urinals, bathing facilities, laundry and dish washing sources, and tens of millions of people are downstream from floating death, or where sewage is simply another irritation while scrounging for food, and education consists of learning which rocks to look under for the next meal or which dump has the least toxic scraps, it is imperative to concede that medicine is only one part of an overall approach to eradicating diseases like Typhoid fever. Food and water security represent both a risk and solution to the problem. Singh mentions that the customary mode of transmission of the disease is by:

“faeco – oral route or urine – oral routes – either directly through hands soiled with faeces or urine of cases or carriers or indirectly by ingestions of contaminated water, milk, food, or through flies. Contaminated ice, ice-creams, and milk products are a rich source of infection.”

Singh also notes the disease is prevalent from July to September, the typical rainy or monsoon season, which also sees an explosion in the fly population. Singh points out that under some conditions, the Typhoid bacilli, which ordinarily die within 48 hours, can be quite hardy, surviving for up to a month in ice and ice cream, and for as long as 70 days in contaminated soil.   

Growth of the bacilli

Singh observes that the Typhoid bacilli grows in milk without making any change in its taste or appearance, and that vegetables grown in sewage farms or if washed with contaminated water also pose a grave risk.  Finally, and most importantly, all of these other causes are secondary to the social factors which support Typhoid fever, such as water pollution, open air defecation and urination, very low standards of proper food and personal hygiene (or any hygiene in some places), and general ignorance about health and safe practices, even in high risk areas which are frequent to contributors to the spread of diseases like Ebola and typhoid fever.  Singh notes that a case is infectious as long as bacilli appear in stool or urine of the infected person.  Temporary carriers usually excrete bacilli for as long as 6-8 weeks. Obviously, in areas where using the local river, stream or brook as a toilet, shared with all of the members of the village or community, and in which all of the community’s clothes and food are washed, and personal bathing is done, it is fairly simple for the disease to become widespread.  Moreover, Singh notes that in 3-4 percent of the cases, infected people continue to excrete bacilli for a year, and in 3 percent of the cases, for longer than one year, even for several years.

Endemic centers for Typhoid fever are:

• Sub-Saharan Africa
• Africa
• China
• India
• Indonesia
• Pakistan
• Bangladesh
• Tunisia
• Morocco
• Vietnam
• Latin America

Symptoms and diagnosis of typhoid fever

According to Crump and Mintz, Typhoid and paratyphoid fever present similar symptoms to acute febrile illnesses, making diagnosis difficult, requiring laboratory confirmation. They note that bone marrow culture is the best test, but in many poor areas, reliance on the 100-year old Widal test is often not helpful as it does not necessarily distinguish between Malaria and Typhoid fever, as well as other cross reacting infections. They indicate blood culture is usually the most practical under the circumstances, although in the poorest areas, blood cultures are often unavailable, too expensive, or not performed consistently.

Often, typhoid fever presents with:

• High fever (often higher than 103 degrees Fahrenheit)
• Severe diarrhea
• Abdominal pain
• “Rose spots”, a rash of small red dots on the chest or abdomen
• Abdominal tenderness
• Bloody stool
• Confusion
• Delirium
• Changing mood which can lead to mental illnesses
• Chills
• Nosebleed
• Severe fatigue
• Lethargy
• Weakness

Severe complications of Typhoid fever include intestinal hemorrhage, intestinal perforation, kidney failure and peritonitis, some or all of which can be fatal. 

Incubation and spread of typhoid fever

The disease at the outset is quiet, with an asymptomatic incubation period of as much as two weeks.

1. During this initial phase, the bacteria invade macrophages and spread throughout the reticuloendothelial system, characterized perhaps by elevation of fever and bacteremia (bacteria in the blood).
2. During the second week, the patient may develop rose spots on the chest and/or abdomen, experience abdominal pain of varying degrees, and develop splenomegaly (enlarged spleen).
3. In the third week, the intestinal inflammation becomes more pronounced and intense, especially in the Peyer’s patches (the site of first response to invasion of the intestinal tract by pathogenic microorganisms). 

Ostrow describes the escalating situation after the third week as follows:

Over the...[initial] 7-14 days the bacteria…spread through the blood stream to other cells in the reticuloendothelial system in the liver, spleen, bone marrow and gall bladder...and … fever, headache and abdominal pain begins. The gallbladder is felt to be ...significant ... for ongoing exposure of intestinal epithelial cells to the pathogen. The inflammatory response to this process of repeated exposure is felt to give rise to the necrosis which is a prominent feature of the disease....This...explains why intestinal bleeding and perforation are the most frequent complications....As the infection progresses the typical changes of sepsis accumulate in the heart, brain and kidneys. If not interrupted this process may lead to circulatory failure and death from overwhelming sepsis.

Treatment of typhoid fever

There are accepted regimens for treatment of Typhoid fever in recent years, mostly focusing on the use of antibiotics.  However, this has not been without substantial controversy, not because antibiotics are not effective but because over time antibiotics become part of the problem, not part of the solution. In their article regarding current concepts in diagnosis and treatment of Typhoid, Bhutta and Dewraj set out some guidelines for successful treatment, which follow through steps which unfortunately are not always possible in those highly endemic areas. As expected, they suggest that speedy diagnosis and antibiotics are the first important step, both of which, as discussed above, pose extraordinarily difficult problems on the field in places like Africa, Bangladesh and in remote or poverty stricken places in Asia, such as parts of India, Thailand, and Indonesia where the disease if frequently spread through drinking water. Since Typhoid looks like other similar diseases, the quick diagnosis is not so simple. 

Assuming the correct diagnosis has been made, they suggest:

“[a]dequate rest, hydration, and correction of fluid-electrolyte imbalance…[a]ntipyretic therapy as required…[to lower fever]”in particular because Typhoid fever usually produces very high temperatures.

Although they suggest paracetamol as an antipyretic, some studies have yielded inconclusive results regarding its effectiveness in the treatment of high fever in children. Butta and Dewraj go on to suggest that, despite general intestinal discomfort, adequate nutrition is very important, and should be attempted at first with:

“a soft, easily digestible diet…unless the patient has abdominal distension or ileus.”

Of course, as with any antibiotic regimen, care must be taken to ensure all of the medication is taken, and it is critical to follow-up with the patient and monitor for further complications and mostly importantly for some relapse, which is common in many cases. Further treatment will therefore include additional antibiotic regimens, often in lower dosages, as the disease will continue to retreat, though making sure it is eradicated requires this diligent attention. It is wise, they suggest, that follow-up includes:

“confirmation of stool clearance in non-endemic areas or in high risk groups such as food handlers.” 

Personal safety 

Butta and Dewraj caution medical personnel to pay very close attention to their own safety, and the safety of other patients and family if the patient remains at or returns home, by having and requiring a very strict regimen of personal hygiene, including hand washing, and limitation, to the extent possible of course, of close contact with others who may be open to infection during the most severe times of infection during the course of Typhoid fever’s persistence.

There are a wide variety of antibiotics that have been used to treat Typhoid fever in different endemic areas, and in some cases, it is the length of a course of treatment that is varied in the severity of the disease in particular patients. Butta and Dewraj, citing a study done in Indonesia over a forty-year period. The study indicated that if diagnosis is made early enough, rapid oral antibiotic treatment can usually manage the disease. They insist, however that:

“Appropriate antibiotic treatment (the right drug, dose and duration) is critical to curing the typhoid with minimal complications.”

They also point out that:

• Treatment with chloramphenicol can have a rate of relapse as high as 5-15%
• Treatment with amoxicillin a rate of relapse of 4-8%
• Newer quinolones and third generation cephalosporins have higher rates of success without relapse

However, it must be noted that as antibiotics are administered in endemic areas, the typhoid there develop drug resistant strains, which in Asia led to the almost universal usage of fluoroquinolones. As expected, new strains of the disease emerged resistant to those drugs, too, and the options for treatment in endemic areas becomes increasingly limited. As they point out, having performed extensive research and studies in 2005,

“Given the signs of rapidly increasing resistance of S typhi to fluoroquinolones, it is imperative that the widespread use of these antibiotics for fever and their availability over the counter are restricted, although it may already be too late.”

Whether or not it is too late may depend on the response the global community decides to implement in the poorest endemic areas of this disease. As discussed below, one branch of preventative care is vaccination.

Vaccines for typhoid fever

As mentioned before, treatment with antibiotics saves lives, but over time vaccines can become more a part of the problem than a long term solution. This is for two reasons:

1. Treatment of any persistent bacteria with antibiotics often gives rise to drug resistant strains, as with Typhoid fever, now appearing as Paratyphoid fever (S. Paratyphi A), and other drug resistant strains. Typhoid fever is an ancient bacterium, and therefore is quite likely very good at adapting.
2. Once antibiotics become available to treat a disease, and deaths are reduced, and lives are saved, finding a global solution becomes less urgent, and the world’s policymakers turn their attention elsewhere to bigger and “more urgent” fires to put out. As a consequence, vaccines become less urgent, and better infrastructure (the real eradicator) even less so.

Initially, vaccines were utilized in Thailand to wipe out Typhoid fever in the 1970s and 1980s, and were mostly successful through vaccination of schoolchildren with “injectable, inactivated, whole-cell vaccines.” The disease was more or less controlled. The program was abandoned because of the high rate of side effects. There are however two newer-generation typhoid vaccines, which have been available for approximately two decades, and have proved extremely safe:

1. Vi polysaccharide
2. Live attenuated Ty21a vaccine

While vaccines can help eradicate a disease, succeeding generations are exposed to the same persistent risks (as in the case of Typhoid, an organism that may be 150,000 years old) unless steps are taken to change the conditions under which endemic areas are in reality petri dishes for growing death.  Brian Ostrow summed it up like this:

[T]yphoid fever remains a major cause of death and disease in the developing world. Its eradication awaits the provision of sanitary water supplies and proper disposal of human sewage. Its eradication would probably be accelerated by programs of mass vaccination in endemic regions.

Conclusion

With growing infection risks from diseases like the Zika virus, doctors around the world in endemic areas of Typhoid fever rush to stay one step ahead of a disease that has been quite adept at surviving by developing drug resistant strains. This “magic bullet” expectation in both patients and medical personnel in the field in some of the most remote and poverty stricken areas of the world, can often contribute as much to the eventual reduction in the efficacy of treatment as anything else. Whether the solution is in a routine of changing antibiotic regimes in specific areas in specific time slots, or continuing to develop new antibiotics to counter this very resilient ancient foe, remains to be seen.  

It has been said that “an ounce of prevention is worth a pound of cure,” and in the case of preventative care for Typhoid fever, this may likely be just as true today as a thousand years ago, except that today, we actually have the tools to do it. Billions of dollars in aid for decades have concentrated mainly on putting a Band-Aid on an open sore as big as Africa, whereas putting a large part of that into the solution, plumbing, education and vaccines, would save millions of lives, and tens of billions in medical costs. In addition, it should be noted that there are hundreds of diseases that thrive under the conditions resolved by good sanitation, so applying these funds to this purpose would be like killing a thousand birds with one stone, something much closer to a magic bullet.

Bibliography

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Bir Singh, “Symposium: Typhoid Fever – Epidemiology,” Journal, Indian Academy of Clinical Medicine, Vol. 2, No. 1 and 2: (2001). 11.

Crump, John A. and Eric D. Mintz. “Global trends in Typhoid and Paratyphoid fever,” Emerging Infections, 50: (2010). 241-246, doi: 10.1086/649541.

Crump, John A., Stephen P. Luby and Eric D. Mintz, “The global burden of Typhoid fever,” Bulletin of the World Health Organization, 82(5): (2004), 346-353.

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Ostrow, Brian, “Typhoid Fever,” Surgery in Africa – Monthly Review, (2006), Retrieved from http://www.utoronto.ca/ois/SIA/2006/typhoid_fever.htm#Epi 

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