Typhoid: Lessons from India and Pakistan

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Title of Paper: Typhoid: Lessons from India and Pakistan

UCLA Department of International Development Studies

By: Hannah Spero

Keywords: typhoid, India, Pakistan, public health, international development

Abstract

Every year, 21.6 million people contract typhoid fever. Of these cases, 7.7 million occur

in South Asia. To make matters worse, this region also has the highest number of typhoid strains

resistant to antibiotics. As the global health community fails to combat this public health crisis,

the tragedy worsens; something must change. This paper examines factors that have led to the

greater proliferation of typhoid and its growing resistance to antibiotic treatments in South Asia.

It reviews the inherent problems related to the medical diagnosis, and treatment of, and

vaccination against typhoid fever. It then examines India and Pakistan case studies that

demonstrate the societal causes for the spread of typhoid. To conclude, the paper reflects on the

lessons that can be learned from the situations of India and Pakistan and proposes the potential

form of a more effective, future public health efforts to combat typhoid internationally.

The Paper

Although typhoid fever was first described in 1829, by Dr. P. Ch. A. Louis, there is a

surprisingly modest amount of knowledge about the disease today1. Typhoid has remained a

major public health concern since Dr. Louis identified its distinguishing lesions, with the British

Medical Journal publishing articles about the disease dating back to 1897, in which it discussed

                                                                                                               1 Robert Edelman, and Myron M. Levine, "Summary of an International Workshop on Typhoid Fever,"

Reviews of Infectious Disease, 8, no. 3 (1928): 329-349.

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an outbreak amongst “natives of India”2. The first vaccine was produced in 1896, and there were

discussions in 1897 of producing an improved vaccine3. More practical vaccines were available

by 1928, with the first trials being administered in 19374. However, those breakthroughs were

nearly a century ago, and little progress has been made since. Efforts to combat the disease have

been plagued with controversy concerning the accuracy of screening tests, the efficacy and

toxicity of vaccines, and the continued failure to implement solutions to the typhoid crisis that

continues today. In order to create an effectual international typhoid treatment and prevention

program, we must examine and learn from the widespread, multi-drug resistant typhoid crises in

India and Pakistan, and we must recognize that solutions can be developed only within the

context of the afflicted society, not simply in the realm of isolated medical research.

It was not until 1884 that a German researcher successfully isolated the bacterium that

causes typhoid fever, Salmonella typhi5. Because this bacterium is of the Salmonella genus,

many think of it as food poisoning, but the infection has sources other than food and is a much

more serious illness than the typical case of food poisoning6. It does, however, enter the body in

the same way as food poisoning: through consumption of food or water contaminated with the

bacterium7. Once a person ingests the bacteria, the human body becomes a reservoir for the

reproduction of the bacteria, and excretes it in his or her fecal matter8. These characteristics of

the disease explain why the level of hygiene is so closely tied to the proliferation of typhoid, and

                                                                                                               2 C.B. Maitland, "Typhoid Fever Amongst the Natives of India," BMJ: British Medical Journal, 2, no. 1921

(1789): 1214-5.  3  Robert Edelman, and Myron M. Levine, "Summary of an International Workshop on Typhoid Fever."  4  W.B. Wherry, T.J. LeBlanc, L. Foshay, and R. Thomas, "The Treatment of Typhoid Fever with

Detoxicated Vaccine," Journal of Infectious Diseases, 43, no. 3 (1928): 189-193; S. Watson Smith, Richard Taylor, and J.V. Pincus, "Immunization Against Typhoid," BMJ: British Medical Journal, 2, no. 4013 (1937): 1139-1140.  

5 Robert Edelman, and Myron M. Levine, "Summary of an International Workshop on Typhoid Fever." 6 Richard B. Hornick, "Selective Primary Health Care: Strategies for Control of Disease in the Developing

World, Typhoid Fever," Reviews of Infectious Disease, 7, no. 4 (1985): 536-546. 7 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever," BMJ: British

Medical Journal, 333, no. 7558 (2006): 78-82. 8 Encyclopedia Britannica Inc., "Typhoid Fever." Accessed March 5, 2012.

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why typhoid is endemic to the developing world. In the developed world, there is infrastructure

to ensure proper sewage disposal and to support hygiene efforts and ensure that anyone carrying

the disease does not spread it to others via food, water, or personal contact9. Even in 1921, the

American Journal of Nursing understood the importance of hygiene when handling typhoid fever

patients, publishing a thorough article about the precautions health care providers must take,

many of which are still relevant today10. These safety measures included the wearing of rubber

gloves when handling anything in contact with a patient’s excretions and other bodily fluids, the

sterilization of all medical instruments after each use, and the thorough washing of a patient’s

plates and utensils after every meal, just to name a few11. In part because of insufficient

infrastructure and inadequate hygienic measures in developing countries, typhoid is endemic to

these countries and spreads rapidly.

The course of the disease and its symptoms also contribute to difficulties in eradicating it.

Once ingested, the bacterium infiltrates the walls of the gastrointestinal tract, where it reproduces

in lymphoid tissue12. Then, within one to three days, it makes its way into the person’s

bloodstream13. Generally, the clinical expressions of typhoid manifest themselves about two

weeks after infection, but the incubation period varies between seven and 22 days14. After that

period, the infected person begins to exhibit symptoms. Almost 75 percent of cases start with a

headache, accompanied by a fever that increases over the first week of this symptomatic

                                                                                                               9 C. Bell, and Alec Kyriakides, Salmonella: A Practical Approach to the Organism and Its Control in

Foods, (Oxford: Blackwell Science, 2002). 10 Harriet L.P. Friend, "Typhoid Precautions," American Journal of Nursing, 11, no. 9 (1911): 712-3. 11 Ibid. 12.Encyclopedia Britannica Inc., "Typhoid Fever." 13 Ibid. 14 S.P. Luby, M.K. Faizan, S.P. Fisher-Hoch, A. Syed, E.D. Mintz, Z.A. Bhutta, and J.B. McCormick,

"Risk Factors for Typhoid Fever in an Endemic Setting: Karachi, Pakistan," Epidemiology and Infection, 120, no. 2 (1998): 129-138; John Rice Miner, "The Incubation Period of Typhoid Fever," Journal of Infectious Diseases, 31, no. 3 (1922): 296-301.

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period15. The fever peaks at around 104 degrees Fahrenheit in the second week, during which

time a person also experiences vomiting, abdominal pain, loss of appetite, lesions, and diarrhea16.

Unfortunately, because these symptoms resemble those of many other illnesses common to

regions where typhoid is endemic, including malaria, tuberculosis, infectious hepatitis, and other

Salmonella bacterial infections, clinical diagnosis can be difficult17.

Difficulties in diagnosing the disease lead to misdiagnosis and improper antibiotic

prescription, because a doctor might mistake typhoid for a different infection. Treating an

infection with an antibiotic that is not effective in killing typhoid contributes to antibiotic

resistant strains of typhoid and allows typhoid to reemerge and spread. Even when the disease is

properly identified as typhoid, strains of Salmonella typhi vary on a regional basis. Each strain

can be more effectively treated with antibiotics specific to the strain, and the misuse of

antibiotics to treat one strain compromises the use of antibiotics to treat other strains18. This is a

problem not only on a local level, but on a global level, as the globalization of the world makes

the spread of new strains of a disease worldwide ever more easy and likely19. As a result, future

treatment becomes more difficult not only for the region in which antibiotics are misprescribed,

but also for areas where those antibiotics had previously been effective for their own specific

regional strain. For example, from 1978-1985, fear arose regarding the efficacy of

chloramphenicol as the drug of choice for treating typhoid patients in Britain20. At the same time,

chlorampheniol resistant strains of typhoid appeared in Mexico, India, Bangladesh, and

                                                                                                               15 R.L. Huckstep, Typhoid Fever and Other Salmonella Infections, (Edinburgh: Livingstone, 1962). 16 Ibid. 17 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever." 18 B. Rowe, E.J. Threlfall, and L.R. Ward, "Does Chloramphenicol Remain the Drug of Choice for

Typhoid?," Epidemiology and Infection, 98, no. 3 (1987): 379-383. 19 Ibid.  20 Ibid.

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Vietnam21. Similarly, when the illness is actually something other than typhoid and requires

different treatment, the over-prescription of antibiotics for typhoid will not treat the true illness,

and creates the opportunity for the true illness to reemerge and spread in potentially multi-drug

resistant forms. Therefore, difficulties in diagnosing typhoid fever jeopardize future treatment of

the typhoid fever and other illnesses as well.

Another complication stemming from the nature of this infectious disease is the

likelihood of reemergence due to carriers who do not exhibit symptoms. Although, ideally,

treatment would entirely kill off the bacteria in a person, that is frequently not the case,

especially in the developing world, where we see a problem of carriers: people who are a

reservoir for the bacteria, but themselves do not produce symptoms22. If someone no longer

suffers symptoms of the illness, they unknowingly spread it to others, adding to the public health

crisis. In the 1920s in the United States, there was an increase in the number of cases, but the

new patients did not acquire the bacteria from abroad, but rather from carrier family members

who had picked up the disease on their travels23. This feature of typhoid fever makes it an elusive

foe for public health workers, and highlights the need for greater hygiene in all communities.

Even if the problems with clinical diagnosis and reemergence are overcome, there still

remain issues related to the available medical technology. These issues can be separated into

three categories: vaccination, screening, and treatment. Although typhoid is not a new disease, its

available vaccines are still questionable, both in terms of their efficacy and their toxicity. There

are two main vaccines up for debate: the killed whole cell vaccine and the Ty21a live attenuated

                                                                                                               21 Ibid.  22 Stanley H. Osborn, and Edith A. Beckler, "Once a Typhoid Carrier, Always a Typhoid Carrier," Journal

of Infectious Diseases, 27, no. 2 (1920): 145-150, 23 Ibid.  

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oral vaccine24. The former is made from a dead virus and is injected into the bloodstream, while

the latter is a weakened live virus that is taken orally in the form of a capsule pill over several

doses25. The first typhoid vaccine, which was produced in 1896, was a primitive version of

today’s killed whole cell vaccine26. Field trials for this type of vaccine began in the 1950s and

1960s in Yugoslavia, Guyana, Poland, and the USSR27. Reviews of Infectious Diseases reported

that these trials yielded an overall efficacy of only 65 percent28. It also cited field trials of the live

vaccine in Nepal and South Africa as being 70 percent effective29. Therefore, the first study

favored the live oral vaccine. However, another study, published by the British Medical Journal,

found an efficacy rate of 73 to 80 percent for the killed whole cell vaccine over three years,

based on field studies in Yugoslavia, Guyana, Poland, the USSR, and Tonga30, and an average

live vaccine efficacy of only about 50 percent, based on data gathered from trials in Egypt, Chile,

Indonesia, Nepal, and South Africa31. Therefore, this second study favored the use of the killed

whole cell vaccine. An analysis of the two studies noted that the averages reported in each study

were a compilation of many averages from regions all over the world, and that the vaccine

efficacy varied greatly from country to country with both vaccines in both studies32. The live

vaccine was 96 percent effective after three years in the Egypt trials, and 45 percent effective in

                                                                                                               24 Myron M. Levine, Catterine Ferreccio, Robert E. Black, Carol O. Tacket, and Rene Germanier, "Progress

in Vaccines Against Typhoid Fever," Reviews of Infectious Disease, 11, no. 3 (1989): S552-S567. 25 Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular

Aspects, (Cambridge, UK: Cambridge UP, 2006).  26 Robert Edelman, and Myron M. Levine, "Summary of an International Workshop on Typhoid Fever."  27 Myron M. Levine, Catterine Ferreccio, Robert E. Black, Carol O. Tacket, and Rene Germanier, "Progress

in Vaccines Against Typhoid Fever."  28 Ibid. 29 Ibid.  30 Eric Engles, Matthew Falagas, Joseph Lau, and Michael Bennish, "Typhoid Fever Vaccines: A Meta-

Analysis of Studies on Efficacy and Toxicity," BMJ: British Medical Journal, 316, no. 7125 (1998): 110-6. 31 Ibid. 32 Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular

Aspects.  

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the Indonesian trials33. The killed vaccine was 84 percent effective in Poland and 51 percent

effective in Yugoslavia34. Clearly there is a connection between the effectiveness of a vaccine

and the context in which we implement it. Both vaccines provide some protection, but greater

research must be done to confer better protection; in general, the efficacy of current licensed

vaccines is less than desirable.

Besides efficacy, we must also consider the toxicity of vaccines. Although the killed

whole cell vaccine had a high global average rate of efficacy, it also had a greater toxicity rate35.

About 16 percent of subjects reported feeling feverish from the vaccine, with 10 percent feeling

ill enough to have to miss work or school36. By comparison, the Ty21a live attenuated oral

vaccine, with a lower averaged rate of efficacy, resulted in only two percent of subjects feeling

feverish and almost no one feeling ill enough to miss work or school37. From this consideration,

the question then becomes whether to value the more effective vaccine with greater side effects

or the slightly less effective vaccine with almost no side effects.

Finally, we must consider the practical mass implementation of each kind of vaccine in a

public health setting. The killed vaccine injection requires more medical equipment than the live

oral vaccine capsule, and more equipment requires more money and medical specialization to

ensure the equipment is handled properly. On the other hand, the oral vaccine consists of three

doses, which might be more difficult for people to remember to take, in contrast to a single

injection of the dead vaccine. Both vaccines have implementation problems; if the flaws in these

vaccines prevent them from stopping the spread of typhoid, we must look for better alternatives.                                                                                                                

33 Ibid. 34 Eric Engles, Matthew Falagas, Joseph Lau, and Michael Bennish, "Typhoid Fever Vaccines: A Meta-

Analysis of Studies on Efficacy and Toxicity"; Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular Aspects.

35 Eric Engles, Matthew Falagas, Joseph Lau, and Michael Bennish, "Typhoid Fever Vaccines: A Meta-Analysis of Studies on Efficacy and Toxicity."

36 Ibid. 37 Ibid.  

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As with the methods of vaccination, there are issues with the accuracy and

implementation of screening tests for typhoid fever. The three tests for typhoid examine stool,

blood, and bone marrow samples. Stool tests require roughly a week to culture, which is a long

time to wait in areas where typhoid is significant38. Also, stool cultures require special lab

facilities to ensure accurate screening and to prevent contamination while awaiting the results39.

Another disadvantage is that a stool sample may be positive for typhoid up to four months after

infection if a person goes untreated, increasing the likelihood of misdiagnosis and unneeded

prescription of antibiotics40. Stool samples probably have a more suitable application in the

developed world as a test for additional confirmation of typhoid. Blood cultures are most widely

used form of typhoid screening and they yield more rapid results than stool samples, but they are

only 60 to 80 percent sensitive, meaning that they yield inaccurate results in roughly one out of

four tests41. Tests of blood cultures are also more likely to reveal a false positive if the person

being tested has been vaccinated for typhoid, which creates questions around the test’s

efficacy42. However, blood cultures are more practical in public health applications due to their

shorter wait time and easier sample collection requirements; collecting blood is easier than

collecting stool. Bone marrow cultures take slightly longer than blood tests, but less time than

stool cultures43. That being said, bone marrow cultures are the most sensitive of the three tests,

with an 80 to 95 percent positive result when typhoid is present; this is because of the higher

                                                                                                               38 Richard B. Hornick, "Selective Primary Health Care: Strategies for Control of Disease in the Developing

World, Typhoid Fever." 39 Ibid. 40 Ibid. 41 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever”; Pietro Mastroeni,

and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular Aspects. 42 Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular

Aspects.  43 Ibid.

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concentration of the organism in bone marrow samples44. Also, bone marrow test are more useful

in identifying specific strains of typhoid compared to blood and stool cultures45. However, like

the stool cultures, bone marrow tests present difficulties in collecting samples when applied in a

public health context. Besides these three tests, there are currently some promising efforts to

produce more rapid, accurate serological testing methods, called Typhidot and Tubex, but these

test are very new and require greater field testing to assess their efficacy and sensitivity46.

Overall, the screening methods present as many debates and information gaps as the

vaccines in the case of typhoid fever. Given that typhoid was identified almost two centuries ago

and that its first vaccine was produced more than a century ago, the lack of effective medical

technology in this area is surprising. There is still so much to be researched in the field of

typhoid. In general, future approaches to typhoid management must involve methods that are not

only effective in ideal circumstances, but also have practical use in public health efforts. Bone

marrow cultures are effective for obtaining positive results, but are not sensible for screening in

developing countries, where the typhoid burden is immediate and there is a lack of training and

facilities to handle those tests. Although blood cultures may be more rapid and require simpler

sample collection methods, those advantages must be weighed against the technique’s efficacy.

Is it worth the possible rate of misdiagnosis? These considerations demonstrate that we must

strive for screening tests that reveal more specific and sensitive results in order to provide proper

diagnosis and treatment, and that are in a form that can be practically implemented in a

developing world setting.

Typhoid fever solutions should be considered in the context of the developing world

because they are almost exclusively relevant to the developing world. Typhoid very rarely

                                                                                                               44 Ibid. 45 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever." 46 Ibid.  

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appears in the developed world, and when it does, the source is a person who has recently

returned from a developing region where typhoid is endemic. Those few cases are treated in a

vastly different setting than cases treated in places like India or Mexico. Developed countries

have greater access to superior medical facilities and treatment47. In addition, developed

countries have built an infrastructure to support personal hygiene, clean food and water, and

sanitation48. Developing regions of the world often lack access to clean water, which makes

clean food and personal hygiene difficult49. Also, the lack of functional sewage drainage means

frequent exposure to dangerous bacteria, like Salmonella tyhpi, from human and nonhuman

sources50. Unfortunately, sometimes there is no distinction between where people get their water

and where they excrete their waste products. With no other alternative water source present,

people are forced to choose whether to risk dying from typhoid or dying from dehydration. The

proliferation of typhoid is inevitable in these conditions.

While more advanced vaccines and screening methods would help slow the spread of

typhoid fever in these regions, the efforts will be useless unless we fix the entire system,

including the poor living conditions of the developing world. Typhoid fever requires societal

solutions, not only medical answers. Resources must also finance projects to create access to

clean food and water as well as build in infrastructure for hygiene and sanitation in the

developing world. These basic conditions are what have made the difference between almost no

typhoid in the developed world and many strains of typhoid endemic to the developing world51.

                                                                                                               47 S.P. Luby, M.K. Faizan, S.P. Fisher-Hoch, A. Syed, E.D. Mintz, Z.A. Bhutta, and J.B. McCormick,

"Risk Factors for Typhoid Fever in an Endemic Setting: Karachi, Pakistan." 48 Ibid. 49 Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular

Aspects. 50 Ibid. 51 Zulfiqar A. Bhutta, Shehla H Naqvi, Raza A. Razzaq, and Badr J. Farooqui, "Multi-Drug Resistant

Typhoid in Children: Presentation and Clinical Features," Reviews of Infectious Disease, 13, no. 5 (1991): 832-6.

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These necessary systemic changes would support the efforts of future advancements in medical

technology.

There is a great loss of life due to the proliferation of typhoid fever. The death toll of the

illness makes it a human tragedy, made even more tragic by the fact that the disease is treatable

and preventable. According to the United States Centers for Disease Control, there are 21.6

million cases of typhoid annually, with over 2 million fatalities52. Unfortunately, those numbers

will likely increase with the emergence of antibiotic resistant strains, making treatment options

less effective and death more likely. Although most of the cases are in the developing world,

typhoid fever and its growing resistance to antibiotics is of global concern. Citizens of the

developed world are directly affected by the situation when they visit regions of the developing

world where typhoid is endemic. Moreover, even when these travelers have received

vaccinations in their developed countries, the current misuse of antibiotics to treat typhoid cases

in developing areas is contributing to the evolution of strains against which current vaccinations

will not protect and which are more difficult to treat even in the medical facilities of the

developed world53. This modern reality is important to keep in mind as we examine typhoid

fever in India and Pakistan, which have the highest prevalence of the illness as well as the

greatest number antibiotic resistant strains; we must learn from the ways in which the public

health crisis unfolded there if we hope to slow proliferation in the future.

India and Pakistan provide a glimpse of the potential future for regions where typhoid is

endemic if we do not change the way in which we manage the disease54. The typhoid situations

in India and Pakistan are dire, with 7.7 million of the 21.6 million global annual cases of typhoid

                                                                                                               52 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever." 53 Zulfiqar A. Bhutta, Shehla H Naqvi, Raza A. Razzaq, and Badr J. Farooqui, "Multi-Drug Resistant

Typhoid in Children: Presentation and Clinical Features," 54 Stella R. Quah, Crisis Preparedness: Asia and the Global Governance of Epidemics, (Stanford, CA:

Walter H. Shorenstein Asia-Pacific Research Center, 2007).

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occurring in South Asia55. This makes the two countries excellent case studies as we look for

practical solutions for the future.

In considering the region’s predisposition for typhoid proliferation, we first examine their

populations. Like most other developing countries, India and Pakistan are experiencing rapid

population growth of already large populations, which would make resource management and

maintenance difficult for even a better equipped country56. Pakistan is growing at a rate between

2 and 3 percent, which means that its population of 173.6 million will double in the next 23 to 35

years57. India’s population is even larger, and is quickly approaching 1.2 billion people58.

In addition, each country’s population has demographic features that make public health

efforts more difficult. A problem specific to India is its varied population density. Although there

is an average of about 300 people per square kilometer, this number is not representative of the

polarization of the population densities throughout the country59. At one end of the spectrum, the

North East District, where Delhi is located, has more than 29,000 people per square kilometer60.

At the other end of the spectrum, the rural districts of Lahul and Spiti have only about two

people per square kilometer61. Each extreme presents it own problems when it comes to

implementing public health solutions for typhoid. In the densely populated parts of India, which

                                                                                                               55 R.L. Rasaily, P. Dutta, M.R. Saha, U. Mitra, M.T.J. Lahiri, and S.C. Pal, "Multi-Drug Resistant Typhoid

Fever in Hospitalized Children: Clinical, Bacteriological, and Epidemiological Profiles," European Journal of Epidemiology, 10, no. 1 (1994): 41-6,

56 Google Public Data Explorer, "World Development Indicators and Global Development Finance." Last modified February 16, 2012. Accessed March 7, 2012. http://www.google.com/publicdata/explore?ds=d5bncppjof8f9_.

57 Stella R. Quah, Crisis Preparedness: Asia and the Global Governance of Epidemics; Google Public Data Explorer, "World Development Indicators and Global Development Finance."

58 Google Public Data Explorer, "World Development Indicators and Global Development Finance." 59 Census of India, Office of the Registrar General & Census Commissioner, "Census of India - India at a

Glance: Population Density." Accessed March 7, 2012. http://censusindia.gov.in/Census_Data_2001/India_at_glance/density.aspx.

60 Ibid. 61 Ibid  

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are among the densest in the world, the spread of disease is rapid and unavoidable62.

Furthermore, having so many people packed together makes it difficult to provide and maintain

human services like sewage drainage systems and clean running water, both of which would help

to slow the spread of typhoid. In rural areas, the problems associated with attempts to provide

services to people stem from the fact that the people are spread so far apart across such a large

area. The distance and isolation make it difficult to implement cost-effective programs for these

people to access medical and other services. In Pakistan, 95 percent of the population lives in a

rural setting. Further impeding the delivery services is the mountainous terrain of Pakistan is a

mountainous country. The difficulties created by these features have been documented in a

study of attempts to provide women’s education and family planning in the region to slow the

infant mortality rate63.

The circumstances that have made India and Pakistan prime for the spread of typhoid

fever do not end with their sheer population size or respective distributions of those populations

over the region, urban and rural. Another demographic characteristic shared by India and

Pakistan, which makes them ideal for the spread of an infectious disease, is the age structure of

their populations64. Their recent rapid population growth has led a large proportion of their

populations being comprised of youth65. As of 2007, one third of the billion-person population of

India was under the age of 1566. That fact is even more startling when we consider that only 6

percent of the population is over the age of 65; these numbers reflect the country’s huge

                                                                                                               62 Richard B. Hornick, "Selective Primary Health Care: Strategies for Control of Disease in the Developing

World, Typhoid Fever." 63 John Stoeckel, "Infant Mortality Trends in Rural East Pakistan," Demography, 7, no. 2 (1970): 235-240. 64 Zulfiqar Bhutta, "Current Concepts in the Diagnosis and Treatment of Typhoid Fever."  65 The World Factbook, "India." Last modified March 1, 2012. Accessed March 7, 2012.

https://www.cia.gov/library/publications/the-world-factbook/geos/in.html; Population Association of Pakistan, "Population Association of Pakistan - Statistics." Accessed March 7, 2012. http://www.pap.org.pk/statistics/population.htm.

66 Stella R. Quah, Crisis Preparedness: Asia and the Global Governance of Epidemics.

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population growth and the struggles it faces in developing67. The imbalance is even more

extreme in Pakistan, where 43 percent of the population is under the age of fifteen, and only 4

percent is over the age of 6568. This demographic shift in both countries toward a greater number

of young people does not bode well for efforts to curb typhoid proliferation in the region.

Younger people are more susceptible to Salmonella typhi for several reasons. First, their bodies

are not fully developed, which makes them more susceptible to disease. Second, because they are

younger, they have less built-up natural immunity to local strains of typhoid compared to the

older generations who have lived in the region longer. In an epidemiological study of typhoid in

Karachi, Pakistan in 1998, the median age of afflicted patients was 5.8 years, with 71 percent of

total subjects being under the age of 1069. This supports the frequent assertion by scholars that in

Pakistan the highest rates of typhoid incidence occur in children of pre-school and school ages70.

Similar statistics have been published in studies of India71. One study that specifically looked at

the demographics of Calcutta residents affect by multi-drug resistant forms of Salmonella typhi

reported the mean age of the subjects to be six years72.

For the young people of India and Pakistan, age is not the only factor that commonly

makes their bodies less developed, and therefore more susceptible to typhoid fever. The living

conditions of the developing world make it difficult to grow a strong body to fight against

infection. The study from Calcutta classified 60 percent of the children as being malnourished or

                                                                                                               67 The World Factbook, "India." 68 Population Association of Pakistan, "Population Association of Pakistan – Statistics”; The World

Factbook, "Pakistan." Last modified February 27, 2012. Accessed March 7, 2012. https://www.cia.gov/library/publications/the-world-factbook/geos/pk.html.

69 S.P. Luby, M.K. Faizan, S.P. Fisher-Hoch, A. Syed, E.D. Mintz, Z.A. Bhutta, and J.B. McCormick, "Risk Factors for Typhoid Fever in an Endemic Setting: Karachi, Pakistan."  

70 P.M.A Shanahan, K.A. Karamat, C.J. Thomson, and S.G.B Amyes, "Characterization of Multi-Drug Resistant Salmonella Typhi Isolated from Pakistan," Epidemiology and Infection, 124, no. 1 (2000): 9-16.

71 R.L. Rasaily, P. Dutta, M.R. Saha, U. Mitra, M.T.J. Lahiri, and S.C. Pal, "Multi-Drug Resistant Typhoid Fever in Hospitalized Children: Clinical, Bacteriological, and Epidemiological Profiles."

72 Ibid.

15    

severely malnourished73. Also, a majority of the patients also could obtain water only from

contaminated public water sources. These realities of the lives of the young people in this region

reinforce the need for societal changes to hygiene infrastructure and access to medical services,

clean water, and adequate food to support medical efforts in this crisis.

The inadequate supplies of clean food, clean water, and health services in the developing

world are further stressed by regional movement and instability; India and Pakistan are no

exception. These issues of movement and instability in relation to the spread of typhoid fever and

drug resistance fall into three main categories: natural disasters, conflict, and scarce resources.

Developing nations like India and Pakistan are especially vulnerable to natural disasters because

of their population size, their population density, their limited access to human services, and the

absence of effective infrastructure to mount and execute large-scale relief efforts. When natural

disasters strike, these countries typically suffer a large number of human casualties, and also a

“large amount of damage to property and other infrastructure, and severe crop loss”74. In India

and Pakistan, the most frequent natural disasters are cyclones, floods and earthquakes, which are

a product of location and lack of infrastructure75. Additionally, volcanic eruptions, fires, droughts

and landslides stress the region76. The lack of development in the area makes all of these things

more devastating than if they had unfolded in a more developed area. Not only are there

casualties as a direct result of a given natural disaster, but there are more casualties in the

aftermath due to the magnification of the hardships associated with living in a region of poverty.

This consequence further increases the ability for a disease to spread, as it becomes even harder

to maintain hygiene, obtain clean food and water, and access appropriate medical services.

                                                                                                               73 Ibid.  74 Joseph P. Stoltman, John Lidstone, and Lisa M. Dechano, International Perspectives on Natural

Disasters, (Dordrecht: Kluwer Academic, 2004). 75 Ibid. 76 Ibid.

16    

The book International Perspectives on Natural Disasters: Occurrence, Mitigation, and

Consequences highlights the occurrence and severity of natural disaster in India, and offers a

clear picture of the frequency of those disasters in creating additional hardship77. In 2001 alone,

India suffered high severity floods and droughts, medium severity cyclones and earthquakes, and

low severity landslides78. In 2004, a 9.0 magnitude earthquake, with an epicenter in Indonesia,

was felt in both India and Pakistan, and caused a tsunami toward the Indian coast79. The Indian

government estimated the death toll from the tsunami at 11,000 people, with 380,000 people

displaced80. In Pakistan in 2010, flooding of the Indus basin following a powerful monsoon

killed 2,000 people and displaced about three million people81. The conditions that develop in the

wake of the displacement of large numbers of people following natural disasters are ideal for the

spread of disease82. First, displaced peoples are uprooted from wherever they were and become

more mobile in an effort to find safety; this means that many people are coming into contact with

new people, and potentially coming into contact with other strains of typhoid for which they

have no natural immunity. Then, when refugee camps form, people are packed closer together

with even more unsanitary conditions. Therefore, in addition to the society changes discussed

above, such as programs for better hygiene, food, and access to water, solutions to curb the

spread of typhoid fever must include improved disaster relief programs to prevent natural

disasters from contributing to the proliferation of typhoid.

The same connections between natural disasters and the spread of typhoid fever can be

seen in the relationship between the infectious disease and conflict. Following the model of the                                                                                                                

77 Ibid. 78 Ibid. 79 Cramer, Brandon. Academic Program Pages at Evergreen, "Tsunami - India." Accessed March 7, 2012.

http://academic.evergreen.edu/g/grossmaz/cramerbd/. 80 Ibid. 81 Kiss, Tamas S. "Pakistan Floods Displace 3 Million." THe Budapest Report, August 4, 2010.

http://www.budapestreport.com/2010/08/04/pakistan-floods-displace-3-million/ (accessed March 7, 2012). 82 Cramer, Brandon, "Tsunami - India."

17    

natural disaster scenario, armed struggle creates warzones where it becomes more difficult to

satisfy basic needs83. In the developing world, conflict magnifies the already existing destitute

conditions. Conflict causes people to flee, which, like the displacement of people by natural

disasters, leads to contact with new people and new strains of diseases like typhoid84. The

immediate surrounding conditions deteriorate, and the probability of contact with disease

increases. Therefore, conflict-resolution is important to any public health solutions where there

are warzones.

In South Asia, India and Pakistan constitute the same conflict, which makes the public

health implications even greater. Since the end of British colonization in the region in 1947,

Pakistan and India have disputed reign over the territory of Kashmir, previously called Jammu

and Kashmir85. The conflict has been described as much a conflict for territory as “a clash of

identities, imagination, and history”86. Pakistanis are entrenched in their belief that not only do

they have the right to the land despite the 1947 partition, but also that the Indian possession of

the land represents India’s refusal to recognize the reality of Pakistan; there are also clashes of

religion in all of these issues between Indian Hindus and Pakistani Muslims87. This is reflected in

the Indian viewpoint on the conflict. Indians say that Pakistan is a “state defined and driven by

its obsession with religion,” and that the conflict stems from the reality that Pakistan “is

unwilling to accept the fact of a secular India”88.

                                                                                                               83 Kaiser Family Foundation, "Study Examines Relationship Between Conflict, Rise In NTDs In Middle

East, North Africa." Last modified March 2, 2012. Accessed March 7, 2012. http://globalhealth.kff.org/Daily-Reports/2012/March/02/GH-030212-Conflict-NTDs-Middle-East.aspx?p=1.

84 Cramer, Brandon, "Tsunami - India.” 85 P.R. Chari, Pervaiz I. Cheema, and Stephen P. Cohen, Perceptions, Politics and Security in South Asia:

The Compound Crisis of 1990, (New York: RoutledgeCurzon, 2003).  86 Ibid. 87 S.G. Kashikar, Dialogue with Pakistan, (New Delhi: India First Foundation, 2004). 88 P.R. Chari, Pervaiz I. Cheema, and Stephen P. Cohen, Perceptions, Politics and Security in South Asia:

The Compound Crisis of 1990.  

18    

Through this conflict, India and Pakistan, two of the countries that suffer from the highest

incidence of typhoid and have the greatest number of multi-drug resistant strains of typhoid are

further destroying the public health situations of each nation. Due to the conflict, living

conditions in Kashmir further deteriorate and people are constantly forced to move, coming into

contact with each country’s strains of typhoid. The public health consequences of the conflict

over Kashmir demonstrate how essential conflict-resolution is to supporting typhoid control

efforts. By resolving conflict, we help to prevent the greater spread of all strains of the disease,

and also put more focus on providing adequate basic human services to the afflicted region.

While governments in the region spend scarce resources on the conflict in Kashmir, they

have made only minimal efforts to control typhoid, consisting of a few small-scale vaccination

programs89. To implement effective solutions to the epidemic levels of typhoid fever in the

developing world, the governments in the region must devote resources to the effort, establish

systems to monitor the sources, proliferation and evolution of the disease, and regulate conduct

that contributes to the spread of the disease. The absence of a typhoid surveillance system leaves

the nations without the information they need to prevent the spread of typhoid or its growing

drug resistance90. The governments of India and Pakistan must establish systems to and the

occurrence of have also aided in the proliferation of typhoid fever through the absence of a

typhoid surveillance system and gaps in government regulations that could control typhoid. Also,

there are simple regulatory measures that both governments could take to hinder disease spread.

In the United States, there are employment restrictions on typhoid carriers. For example, typhoid

carriers cannot be employed in the food industry, especially involving food preparation91. If

                                                                                                                89 John Stoeckel, "Infant Mortality Trends in Rural East Pakistan."

90 S. Akbar Zaidi, "Health Research in Pakistan," Economic and Political Weekly, 30, no. 6 (1995): 307-8.  91 S.P. Luby, M.K. Faizan, S.P. Fisher-Hoch, A. Syed, E.D. Mintz, Z.A. Bhutta, and J.B. McCormick,

"Risk Factors for Typhoid Fever in an Endemic Setting: Karachi, Pakistan."

19    

India and Pakistan adopted similar regulations, they would eliminate many of the cases of

typhoid contracted in the workplace and from commercially prepared foods.

In addition to inadequate infrastructure and government regulation to aid the control of

typhoid in the region, there also exist major gaps in the countries’ medical systems. According to

the World Health Organization, there are 8.1 doctors and 5.6 nurses/midwives for every 10,000

people in Pakistan, which has a population of 173.6 million92. India, with a population of nearly

1.2 billion, has six doctors and 13 nurses/midwives for every 10,000 people93. Even ignoring the

overwhelming health crises of the two countries, these numbers reflect a debilitating shortage of

medical personnel; there simply are not enough medical workers to come close to operating

satisfactory medical systems in India and Pakistan. The shortage creates several problems. First,

because of the high rates of typhoid and other disease, it is impossible for doctors to see

everyone who is sick94. Second, this shortage puts pressure on doctors to come up with quick

diagnoses and treatments; misdiagnosis is not unlikely, especially in the case of typhoid where

many other common diseases present the same clinical symptoms. Third, because of the large

number of patients, doctors cannot personalize treatment options; instead, doctors resort to “one

size fits all” treatments for diseases of major public health concern, which results in less effective

and more problematic treatment. Because strains of typhoid vary regionally, prescribing the same

antibiotic treatment for all patients is not a sustainable way to treat the disease. This practice is a

major contributor to antibiotic-resistant typhoid in India and Pakistan. When doctors choose not

to tailor prescriptions to attack the regional strain of typhoid present in the patient, and instead

prescribe a more general antibiotic, they slowly contribute to the antibiotic resistance of the

                                                                                                               92 World Health Organization: Global Health Observatory, "Pakistan: Health Profile." Accessed May 18,

2012. http://www.who.int/gho/countries/pak.pdf.  93 World Health Organization: Global Health Observatory, "India: Health Profile." Accessed March 7,

2012. http://www.who.int/gho/countries/ind.pdf. 94 S. Akbar Zaidi, "Health Research in Pakistan."  

20    

regional strain. This development forces doctors to look for other treatment options once the

strain is multi-drug resistant and the former general antibiotic treatment is rendered useless. With

more medical personnel and a shift to regional-specific antibiotic treatments for typhoid fever,

these countries would slow the growing number of antibiotic resistant strains, and would reduce

the number of people who contract typhoid by reducing the incidence of typhoid reemergence.

In order to make those changes in the medical systems of India and Pakistan, we must

understand the current mentality of the systems, both on the side of the patients and the medical

professionals. Even if doctors began to treat typhoid with more regionally specialized

prescriptions, the change is useless if patients do not understand how important it is for them to

take their antibiotics properly. Unfortunately, that fact is not limited to the developing world.

Many people in the developed world and the developing world misuse their antibiotic

prescriptions95. When a patient does not take antibiotics at the proper intervals, the antibiotics are

not effective. Instead of being killed, the virus survives, adapts, and becomes resistant to the

antibiotic in the future96. Similarly, because people often begin to feel healthy after a few days of

their antibiotic regimen, they stop taking their antibiotics, allowing the virus to survive and

become stronger. When the virus reemerges, the same antibiotic treatment will not be as

effective97. Patients are focused on feeling better faster, and they do not think of their treatment

as something that needs to be sustainable on a society level. An education campaign is necessary

to teach people about the importance of proper antibiotic use in order to make a long-term

typhoid treatment effort successful.

                                                                                                               95 Ibid. 96 Pietro Mastroeni, and Duncan Maskell, Salmonella Infections: Clinical, Immunological, and Molecular

Aspects. 97 Ibid.

21    

Part of educating the public in these areas where typhoid is endemic requires changing

the mentality developed by many of the medical professionals during their training and practice.

At medical schools in Pakistan, doctors are educated to provide basic clinical care rather than

comprehensive evaluations98. To make matters worse, much of their educational material is

similar to that taught in the developed world; Pakistani medical students read about typhoid fever

in the context of the developed world, where the infection is rare99. Physicians receive a generic

education that is unrelated to the circumstance that they will be practicing medicine in the

developing world amid a major public health crisis100. Another consequence of the focus on

training doctors to provide basic, generic care is that medical research is not a for medical

professionals in India or Pakistan101. In addition, many doctors and medical researchers in these

countries see research as an “unaffordable luxury”102. This attitude may be traced back to the

shortage of doctors. Because doctors are in such high demand, both nations are looking only for

doctors with a medical license to provide basic treatment. Compared to the developed world,

there is far less incentive to fund and produce medical research. Dr. Zuberi of Pakistan puts it

best when he explains, “Research is not a prerequisite for appointment or promotion and there is

not academic or financial rewards. You really have to be crazy to do research in this country, for

it is something that is looked down upon and considered a waste of time which should be spent

seeing more patients and making more money”103. This mentality must be changed if we hope to

effectively combat not only typhoid fever, but also any public health crisis in the future. The

support of the medical community is vital to efforts to implement typhoid control programs. One

                                                                                                               98 S. Akbar Zaidi, "Health Research in Pakistan." 99 Ibid. 100 Ibid. 101 Ibid. 102 Ibid. 103 Ibid.  

22    

of the most effective things we can do is educate doctors in the context of the setting where they

will be working, and also teach them about the importance of developing sustainable treatment

methods. The frequency of multi-drug resistant typhoid strains can be reduced, but any

successful programs will require a collaborative, integrated partnership with the medical

community that focuses on tailoring and improving treatment in the particular region.

The numerous factors that have made India and Pakistan prime locations for the spread of

typhoid fever and the development of drug resistance strains yield many lessons that must be

applied globally to public health efforts against this infectious disease. The task may seem

daunting in light of the situations in these two countries, but typhoid may be controlled if we

focus our efforts on curbing the spread of typhoid, and doing so in a way that preserves the

integrity of its methods; in other words, it must be a long-term sustainable solution, not a quick

fix. Moreover, the solutions must be practical in the sense that they can be easily implemented in

a developing world context; any solution will useless if it is not user-friendly for the developing

world.

There are lessons we can learn from the cases of India and Pakistan. More research must

be conducted in the areas of vaccines and screenings. We can and must develop more effective,

less toxic vaccines, preferably in more practical forms that do not require excessive equipment or

multiple doses. Also, by committing resources to finding more specific and accurate screening

tests for typhoid, we may develop means to better identify cases in general, and also treat

infections with greater specificity based on local strains, as opposed to the same treatment for all

strains. As noted, treatment methods can also be made more effective if the public understands

the importance of proper antibiotic use and if doctors adjust their attitudes to consider more

23    

sustainable ways to treat typhoid and to avoid contributing to new drug resistant strains of

typhoid.

All of these solutions are on a micro-level, in that they look to address typhoid in the

context of the patient/doctor relationship. However, the global typhoid crisis requires more

comprehensive effort geared towards the societal factors that have aided in the proliferation of

today’s typhoid crisis. Solutions must include development efforts to increase all of the

following: clean food, clean water, hygiene infrastructure, functional sewage drainage systems,

government disease surveillance, medical professionals, medical support staff, and adequate

disease research laboratory facilities. This list is not exhaustive, as it must include all reforms

and initiatives that improve living conditions and thereby make people stronger and better able to

fight off typhoid and other diseases, that provide access to facilities for proper treatment in the

case that they do contract typhoid fever, and eradicate the conditions that allow typhoid to thrive

and spread.

There is great potential for defeating this disease and ending this crisis, especially as

people begin to realize that public health concerns are relevant globally, not just to the

developing world. Notwithstanding the global relevance of typhoid, however, the treatment and

prevention systems we create must address the disease in the setting in which our programs must

be implemented: the developing world with its many barriers to success in this fight.

24    

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