What is Typhoid Fever & Why Are Researchers So Worried About A Recent Outbreak In Pakistan?

Bacterial infection has always plagued human history, and it likely always will.

Organisms like Tetanus, Anthrax, Tuberculosis, Cholera, Botulism, Syphilis, E. coli, and Typhoid fever have taken countless human lives over the past 200 years alone.

Thanks to the invention of antibiotics, bacterial infections have become far less severe over the past 70 years. Recently, however, these organisms are develping resistance the antibiotics we use against them.

Eventually we'll run out of options to use against bacterial infections, allowing them to wreak havoc on modern society as they did in the era preceeding the invention of antibiotics.

The first big post antibiotic outbreak could be from a common form of Typhoid fever found in Pakistan.

Drug Resistance

Drug resistance has been around since the mid 1950’s, but didn’t start to pose significant problems until recently. As a bacteria becomes resistant to one strain of antibiotic, doctors would simply switch to another. As time goes on however, bacteria are becoming better at resisting our medicines, and drug resistance is now an ever increasing issue in the medical industry.

Salmonella typhi, the bacteria responsible for Typhoid fever is one of the most virulent bacterial infections known. Since the 1980’s, S. typhi has gradually become resistant to antibiotics.

Recently, a new strain of S. typhi has been appearing in areas around Pakistan that can resist all but the last line of antibiotics used to treat it. Researchers are calling this strain “extensively drug-resistant typhoid” (XRT).

If XRT resists our last line of defence, we will no longer be able to battle and contain outbreaks.

What Is Typhoid Fever?

Typhoid fever comes from a Salmonella bacterium infection. There are over 2500 different types of salmonella, however, the most common human illness from salmonella comes from the Salmonella enterica species.

Salmonella can be separated into 2 categories: 

1. Non Typhoidal Salmonella

This is the type of salmonella infection we often hear about as outbreaks in our food, or that can be transmitted through raw eggs or meat. It can spread between animals including livestock and domesticated pets, and humans. This type of salmonella infects only our gastrointestinal tissue, causing moderate to severe diarrhea. Salmonella enterica is the most common species of non-typhoidal salmonella.

2. Typhoidal Salmonella

This infection is much more severe. These strains of salmonella can puncture the gastrointestinal lining, allowing various compounds and microorganisms to enter our bloodstream and infect other organs (including salmonella itself). The main species responsible for this is Salmonella typhi.

Typhoid fever is the name given to any condition involving the infection of typhoidal salmonella infection.

Other strains of Salmonella can cause very similar symptoms (though ultimately less severe). These are referred to as Paratyphoid Salmonella. This is caused by the species S. paratyphi A, B, or C.

What Are The Symptoms Of Typhoid Fever?

High-Grade Fever

Splenomegaly

Rash (characteristic rose spots)

Fatigue & Malaise

Diarrhea OR Constipation

Leukopenia

Anemia

Abdominal pain

How Is Typhoid Spread?

Salmonella typhi only infects humans, and is spread through human faeces. This means that transmission is especially virulent in areas with poor hygiene and waste disposal. It can also be transmitted through food handled by infected individuals who didn’t wash their hands effectively or from flies travelling from faeces to food.

In areas like India and Pakistan where Salmonella typhi is endemic, it’s common to see areas with overpopulation and poor sewage systems contaminating drinking water and crops. This provides a perfect breeding ground for Salmonella of all kinds. 

It’s also possible for Salmonella typhi to spread from infected individuals who are showing no symptoms. The first case of this was a woman aptly nicknamed Typhoid Mary.

Mary was a carrier of Salmonella typhi, but showed no symptoms of the disease.

She was a chef, and was thought to have transmitted the bacteria to over 50 people through the food she prepared them. Some of these people ended up dying from the illness.

Contaminated waterways like this are a perfect breeding ground for drug resistant microbes like Salmonella typhi

How Dangerous Is Typhoid Fever?

The CDC lists typhoid fever as a life threatening illness. As many as 21.5 million people are infected every year resulting in the death of 130 000 to 210 000 people each year. This is about 1% of those infected. It's important to note that this is WITH effective antibiotics available. Without these, the numbers would likely be MUCH higher. 

Typhoid fever results in death in about 20-25% of those infected (without antibiotics), and if it isn’t treated, the fever can last for several weeks or months.

Even those whose symptoms disappear can still be infected with Salmonella typhi, allowing them to transmit the illness to others more easily.

Without antibiotics, the death toll based on this fatality rate could be closer to 4.3-5.3 million deaths each year.

How Does Typhoid Fever Work?

Salmonella typhi is considered a gram negative bacteria. It's rod shaped, and has a set of long flagella that allows it to control its movement to reach more ideal places in the body.

Upon entering the body, Salmonella typhi attaches to the epithelial cells lining the gastrointestinal tract. Here, it injects them with a cocktail of toxins (effector proteins) directly into the intestinal cells. These effector proteins manipulate the cells function, causing it to engulf the invading salmonella. Once inside, it secretes other effector proteins to protect itself from being digested, allowing it to grow and multiply inside the cell. 

Most salmonella remains in the gastrointestinal tract for the duration of their lifespan, however, Salmonella typhi can spread into the blood, and begin infecting other organs as well. This is what makes typhoid fever so devastating. It often leads to sepsis, and death. 

Treating Typhoid

The ability for typhoid to enter the cells and multiply (much like a virus) makes it especially difficult to treat since the antibiotics used need to be able to penetrate the infected cells.

We currently have 3 main antibiotics we can use to treat typhoid fever: 

1. Ceftriaxone

2. Fluoroquinolones (such as Ciprofloxacin)

3. Azithromycin

In severe cases, corticosteroids like prednisone are often used to control symptoms. 

Mortality is most common in those who are malnourished, making it especially important to ensure adequate nutrition in those affected. 

The Significance of the Typhoid Outbreak in Pakistan

Salmonella infection, including Typhoid Fever, is common in Asia. Up to 75% of infections in the United States are the result of overseas travel to places like Southeast Asia. Pakistan and India are especially common places to contract these infections.

The recent outbreak in Pakistan is different than most salmonella infections because the infecting strain is resistant to all but azithromycin, the last line of defence against Salmonella typhi. If this bacterium manages to develop resistance to this class of antibiotic, there will be no treatment options left to manage the infection. This also means there are no other options for those who may be allergic to azithromycin, resulting in further complications, or an inability to use the drug at all. 

The conditions present in the epicenter of this outbreak, Hyderabad, have allowed a perfect storm of Typhoid adaptation and infection. The city is overpopulated, containing an estimated 6 million people, and has poor sewage elimination. This allows the sewage to overflow into rivers and streams, contaminating drinking water sources.

This outbreak is not localised to these regions, however, and will likely spread globally, replacing weaker strains of the bacteria, and spreading throughout both the developed and undeveloped world. A case has already been detected in the United Kingdom.

If this strain worsens, we’re likely to experience similar fatality rates to pre-antibiotic eras, which was about 1 in 4 infected.

Tips For Preventing A Global Typhoid Fever Epidemic:

1. Vaccination

Vaccines are available for preventing the spread of this bacteria, which unfortunately is undergoing a wide degree of conspiracy in the infected regions of the world. Rumours of “poisoned vaccines” are circulating Pakistan, causing people to refuse the vaccination attempts. This is not a new concept, as vaccines have been at the center of conspiracy theories in the United States, Asia, and the Middle east. The New York Times reported a few years ago about a series of attacks on Polio vaccination teams in Pakistan based on a similar conspiracy.

The vaccination will likely become more common as the potential threat this illness poses to global health becomes better understood. The vaccine has a short duration, however, only lasting about 5 years.

2. Antibiotic Development

New treatment options are also important. We need to continue the search for new antibiotic candidates for treating this infection so that new treatment options can be developed. A list of ethnobotanical treatments for typhoid is listed below. From ethnobotanical information like this, researchers can begin to isolate compounds, and develop new and effective antibiotics to treat those affected by Typhoid fever before it’s too late.

3. Improvements in Hygiene & Sanitation Infrastructure

One of the long term improvements that needs to be made to reduce the chances of contracting typhoid fever is the sanitation infrastructure. Salmonella typhi spreads from feces coming into contact with the gastrointestinal tract. This is commonly the result of poor sewage management in large cities, allowing the bacteria to move from contaminated waste to drinking water. Improving these sewage networks, treatment plants, and clean water sources can significantly reduce the chances of infection.

Additionally, personal hygiene improvements, such as sanitising the hands before preparing or eating meals, and after using the toilet go a long way in preventing the spread of this illness.

Herbs For Typhoid Fever

Traditionally there are many different herbs indicated for Typhoid according to various regions and indigenous cultures. Over the past 60 years, since the invention of antibiotics, we have stopped relying on plants in the treatment of Typhoid fever and other forms of Salmonella. 

With drug resistance increasing at an alarming rate, we need to begin considering other treatment options for this condition. From here, we can identify herbs that are effective for treating or managing the condition, as well as investigate new drugs from these plant sources to combat XDR Typhoid and other superbugs just like it. 

Although antibiotics should always be used whenever possible for typhoid fever, in the event that it doesn't work, we need backup options. Below is a list of plants with traditional indications for typhoid fever. Anything with evidence to support these claims is listed beside it. The vast majority of the evidence listed is in vitro, or animal testing only.

This is to serve as a starting point for developing new treatment options for typhoid fever.

Ethnobotanical Treatments For Typhoid

Botanical Name	Common Name	Scientifically Validated?
Ageratum conyzoides	Billygoat-Weed	[3]
Aspilia africana	Aspilia	[4]
Azadirachta indica	Neem	[5]
Balanites aegyptiaca	Desert Date	[12]
Bidens pilosa	Spanish Needle	[6]
Carica papaya	Papaya	[7]
Carthamus tinctorius	Safflower	[8]
Carum carvi	Caraway	[8]
Cupressus lusitanica	Mexican White Cedar	[15]
Delphinium vestitum	Clothed Delphinium	NA
Dyschoriste perrottetii	Bidi-Diyan	NA
Elmerillia papuana	Elmerillia	[6]
Emblica officinalis	Gooseberry	[8]
Emilia coccinea	Scarlet Tasselflower	[9]
Eremomastax speciosa	Unknown	NA
Erigeron floribundus	Asthmaweed	[10]
Eucalyptus globulus	Eucalyptus	NA
Eugenia caryophyllata	Clove	[5]
Ficus sur	Cape Fig	NA
Ficus thonningii	Strangler Fig	[11]
Gentianopsis vvedenskyi	Erect Gentian	NA
Lamium album	White Nettle	NA
Lawsonia inermis	Henna	[8]
Moringa oleifera	Moringa	[12]
Musa acuminata × balbisiana	Banana Flower	[13]
Ocimum sanctum	Tulsi	[5]
Onosma hispida	Bristly Onosma	NA
Plumbago zeylanica	Ceylon Leadwort	[8]
Psidium guajava	Guava	[14]
Pteridium aquilinum	Eagle Fern	NA
Senna alata	Candle Bush	[16]
Swertia petiolata	Swertia	NA
Tamarindus indica	Tamarind	[8]
Terminalia belerica	Bahera	[8]
Terminalia chebula	Harra	[8]
Zehneria scabra	Zehneria	NA

Author Bio:

Justin Cooke is a medical herbalist, and the founder of The Sunlight Experiment. He has a passion for scientific research and discovery is what motivates him to produce content like this everyday.

He earned a Bachelor of health sciences (BHSc) degree in 2018, and currently writes for a number of prominent health and medical blogs.

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References

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