AN EPIDEMIOLOGICAL STUDY ON CERTAIN WATER BORN DISEASES OF DEHRADUN AND HARIDWAR DISTRICT OF UTTARAKHAND

A PROJECT REPORT SUBMITTED FOR THE PARTIAL FULFILLMENT OF THE DEGREE OF

MASTER OF BUSINESS ADMINISTRATION IN HEALTH CARE SERVICES

FROM SIKKIM MANIPAL UNIVERSITY

By

Dr. VISHWA DEEPAK BAMOLA Roll No. 521039470 MBA (HCS) 4th Semester
Dr. V D BAMOLA 1 Roll No. 521039470

ACKNOWLEDGEMENTS

I am extremely grateful to my guide Dr. P Mohanty for his able guidance, critical comments and valuable suggestion for the completion of this project. I am also grateful to all faculty and staff of my study centre of the program for their kind cooperation and help. I am grateful to all inhabitants /volunteers of the area of my study for their cooperation, providing samples & necessary information during study. I would like to express my special thanks to CMO/CMS, Doctors and paramedical staffs of different hospitals for their kind help during data and sample collection. Especially I would like to thanks doctors and staff of Combined Medical Institute Dehradun, Doon Hospital Dehradun, Ahuja Pathology Dehradun, Goyal Pathology Dehradun, Coronation Hospital Dehradun, Chabra Pathology Dehradun, City Hospital Haridwar, District Hospital Haridwar, Ganga Valley Hospital Haridwar etc. I would like to express my appreciation to my family and friends for their moral support and constant encouragement.

Dr. VISHWA DEEPAK BAMOLA Roll No. 521039470 MBA (HCS) 4th Semester

Dr. V D BAMOLA

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CERTIFICTE

To Whom It May Concern

This is to certify that the project entitled An Epidemiological Study on Certain Water Born Diseases of Dehradun and Haridwar District of Uttarakhand submitted by Dr. Vishwa Deepak Bamola, for the partial fulfillment of the degree of Master of Business Administration in Health Care Services, has been carried out under my supervision.

Supervisor

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CONTENTS

CHAPTERS

PAGE NO

Chapter

1.0 1.1 1.2 1.3 1.4

GENERAL INTRODUCTION Typhoid Fever Jaundice Diarrhea Cholera

1-2 3-4 5-6 7-8 9-10

Chapter

2.0

MATERIAL AND METHOD

11-12

Chapter

3.0 3.1 3.2

RESULTS Month wise incidence Sex wise incidence

13-15 13-14 14-15

Chapter

4.0 4.1 4.2 4.3 4.4

DISCUSSION Typhoid Fever Jaundice Diarrhea Cholera

16-28 16-18 19-21 22-24 25-28

Chapter

5.0

SUMMARY AND CONCLUSIONS

29-31

Chapter

6.0

REFERENCES

32-33

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Chapter 1.0 GENERAL INTRODUCTION

Water-borne diseases are the illness caused due to the contamination of drinking water by pathogenic micro-organisms. The causative agents of water-borne diseases may be bacteria, viruses and protozoan. Over the past decades, water-related human health issues have become increasingly comprehensive, with the emergence of new water-related infectious diseases and the re-emergence of ones already known. The emerging and reemerging infectious diseases have recently proven to be the biggest health threat worldwide and they contribute between 70- 80% of health problems in developing countries. Several water-borne diseases such as cholera, diarrhea, and typhoid are the leading causes of morbidity and mortality. The burden of these diseases is most felt in almost all tropical areas of the world. Some of the major causative agents of water-borne diseases are Salmonella typhi, responsible for typhoid fever, Vibrio cholerae, responsible for cholera, Escherichia coli, responsible for most dysentery, Giardia and Cryptosporodia species are causative agents of most of the Gastroenteritis diseases reported around the world. Viral agents like hepatitis species are also among the worst causative agents of water-borne diseases in Asia, Africa and South America. There are numerous types of other microorganisms responsible for water-borne diseases. Clean water is essential for healthy living. Adequate supply of fresh and clean drinking water is a basic need for all human beings on the earth. Millions of people worldwide are deprived of clean drinking water. Industrial growth, urbanization and the increasing use of synthetic organic substances have serious and adverse impacts on freshwater bodies and leads to health hazards commonly known as Water Borne diseases.

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Water-borne diseases are mainly attributed to water that has been contaminated by human, animals or chemical wastes. The World Health Organization has reported that water-borne diseases kill more people more than any other disease in the world (WHO, 2009). Worldwide, it has been shown that water-borne diseases are responsible for over 12 million deaths a year. This is mainly due to poor sanitation facilities and unsafe drinking, washing, and cooking water [Hinrichsen, 1998]. Millions of people throughout the world have little access to sanitary waste disposal infrastructure or clean water. As a result, millions of people are at risk because of lack of access to safe drinking water and adequate sanitation facilities. In developing countries four-fifths of all the illnesses are caused by water-borne diseases. Globally some 1.1 billion people still lacking access to improved drinking water sources and some 2.4 billion to adequate sanitation. There are strong evidence that water, sanitation and hygiene-related diseases account for some 2,213,000 deaths annually and an annual loss of 82,196,000 Disability (Bloland et. al 1999). Diarrhoea is the leading cause of childhood death. Diarrhoeal diseases are prevalent in many countries mainly due to inadequate sewage treatment. About 4 billion cases of diarrhoeal disease occur every year, causing 3- 4 million deaths among children (Hinrichsen, 1998). All the studies conducted in different parts of the world clearly showed that waterborne diseases are a serious health threat, particularly in developing countries and causing a great burden to the health system. The rationale of this study includes the assessment of the burden of water-borne diseases in the area which can provide the useful information for health planning, management and evaluation of health management plans in these districts.

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Chapter 1.1 Typhoid fever

Typhoid and paratyphoid enteric fever are acute, generalized infections caused by Salmonella typhi and Salmonella paratyphoid respectively. The main sources of infection or carriers are contaminated water and food. Once the bacteria enter in the body they multiply and spread from the intestines into the bloodstream. In untreated patients complications may be numerous, affecting practically every body system, and can even include perforation of the intestine with haemorrhage. Complications account for the mortality rate of 7% to 14%. The annual incidence of typhoid is estimated to be about 17 million cases worldwide. Typhoid fever caused by Salmonella typhi is a public health problem in many countries with an estimated global incidence of 60 million cases and 500,000 deaths annually (Levine, 1998, Parry et al 2008). This problem is especially pronounced in the developing countries due to several interrelated factors including variable efficacies of currently available vaccine, unplanned urbanization with the growth of urbanized slums, lacking safe water supply and sanitation facilities etc (Thong et al 1994, Levine & Levine 2004). Salmonella typhi is a gram-negative bacterium belongs to the genus Salmonella and family Enterobacericea. S. typhi is rod-shaped with a length of 2-3 m and a

diameter of 0.4-0.6 m (Le Monor, 1981). It grows best under aerobic conditions but may also grow anaerobically. The temperature range for the growth of S. typhi is from 4 to 40C and the optimum is 37C (Smith, 2007). S. typhi can survive about a week in sewage contaminated water and remains viable in fecal materials for 1-2 weeks (Smith, 2007). Human hosts ingest S. typhi with contaminated water or food. After ingestion S. typhi passes through the upper gastrointestinal tract to the small intestine where it attaches

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to the tips of the villi (Hoffman, 2001, Parry et al 2008), probably via cystic fibrosis transmembrane conductance regulator (CFTR)-receptors (Pier et al, 1998) and either invades the intestinal mucosa directly or multiplies several days before invading, a phenomenon probably regulated by genes located in the Salmonella Pathogenicity Islands (Everest et al, 2010) in the genome of S. typhi. After invasion, typhoid organisms reach the lamina propria (Ivanoff et al, 1994) and via the M cells of the intestinal Peyers patches (PP) migrate into mesenteric lymph nodes where they multiply (Everest et al, 2010). Bacteria released into the circulation via the thoracic duct disseminate (Hoffman, 2001, Ivanoff et al, 1994, Everest et al, 2010) widely before being taken up by macrophages lining the sinusoidal walls of the liver, spleen, and bone marrow. Predominant cell types induced by S. typhi are macrophages and T lymphocytes (Hoffman 2001, Everest et al, 2010). At the sites of localization of S. typhi the endotoxin of S. typhi induces macrophages to produce an array of cytokines, including tumor necrosis factor (TNF) and interferon, and various arachidonic acid metabolites (Hoffman, 2001). Cytokines alone, when acting locally at the sites of their production or when disseminated via the blood stream, can mediate the development of fever (Newton & Krishna, 1998), intestinal necrosis (Everest et al, 2001), hepatic dysfunction (Tiegs, 1997), pneumonitis thrombosis vascular instability leading to shock bone marrow depression (Hoffman 2001), and altered consciousness (Newton & Krishna, 1998).

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Chapter 1.2 Jaundice

Jaundice itself is not a disease, but rather a symptom of an underlying pathological process that occurs at some point along the normal physiological pathway of the metabolism of bilirubin. Jaundice is a yellowish discoloration of the skin and eyes caused by increased levels of bilirubin in the extra cellular fluids. Old or damaged red blood cells are constantly being removed from the circulation, mainly by the spleen. During this process hemoglobin is broken down into a dark greenish yellow pigment called bilirubin. Bilirubin is then carried in the bloodstream to the liver and is excreted into the intestine as a component of bile. If bilirubin cannot be excreted into bile quickly it builds up in the blood. The excess bilirubin is deposited in the skin resulting in the yellowish discoloration called jaundice (Guyton and Hall, 2006). Jaundice, also known as Icterus is a yellowish discoloration of the skin and eyes caused by hyperbilirubinemia (increased levels of bilirubin pigment in the blood). Hyperbilirubinemia subsequently causes increased levels of bilirubin in the extra cellular fluids. Old or damaged red blood cells are constantly being removed from the circulation, mainly by the spleen. During this process hemoglobin is broken down into a dark greenish yellow pigment called bilirubin. Bilirubin is then carried in the bloodstream to the liver and is excreted into the intestine as a component of bile. If bilirubin cannot be excreted into bile quickly it builds up in the blood. The excess bilirubin is deposited in the skin resulting in the yellowish discoloration called jaundice (Guyton and Hall, 2006). When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin, jaundice may occur. High levels of bilirubin in the blood may result from problems originating either within the liver or outside the liver.

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Damage to the liver such as inflammation or scarring, can impair its ability to excrete bilirubin into bile. Alternatively, the bile ducts may be blocked by a gallstone or a tumor. Less commonly, overproduction of bilirubin due to excessive breakdown of red blood cells can overwhelm the liver with more bilirubin than the liver is capable of processing. Overproduction is most common in newborns with jaundice. Jaundice is classified into three categories depending on which part of the physiological mechanism affected. The three categories are Pre-hepatic (pathology occurs prior to the liver), Hepatic (pathology located within the liver) and Post-Hepatic (pathology is located after the conjugation of bilirubin in the liver) In jaundice, the skin and whites of the eyes appear yellow. Urine is often dark because excess bilirubin is excreted through the kidneys. People may have itching, lightcolored stools or other symptoms depending on the cause of jaundice. For example, acute inflammation of the liver (acute hepatitis) may cause loss of appetite, nausea, vomiting, and fever. Blockage of bile may result in abdominal pain and fever.

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Chapter 1.3

Diarrhea
Diarrhoea is a symptom of infection by a host of bacterial, viral and parasitic organisms most of which can be spread by contaminated water. Diarrhoea is frequent discharge of watery faeces from the intestines, sometimes containing blood and mucus. Diarrhoea due to infection may last a few days, or several weeks, as in persistent diarrhoea. Persistent diarrhoea may result in severe dehydration and shock. Severe diarrhoea may be life threatening due to fluid loss in watery diarrhoea, particularly in infants and young children, the malnourished and people with impaired immunity. Diarrhoea is a concomitant of many infectious diseases, especially typhoid fever, bacillary or amoebic dysentery, and cholera. Diarrhoea due to infection is widespread throughout the developing world. In Southeast Asia and Africa it is responsible for 8.5% and 7.7% of all deaths respectively. In almost every developing country, diarrhea and respiratory infection are the first and second most common causes of illness and death among children under 5 years old. Diarrheal disease causes about 3.2 million child deaths annually. In some countries, children suffer an average of eight or nine diarrheal episodes a year (compared with a global average of three per child per year) (WHO, 2009). As much as 13 percent of a child's life may be spent ill with diarrhea. Repeated and prolonged bouts contribute to undernourishment, which in turn increases the severity and duration of future diarrheal episodes. Diarrhea is caused by bacterial, viral, and parasitic infestations transmitted through water, food, and contact with fecal matter. Preventing diarrhea requires better sanitation and more abundant, cleaner water supplies, as well as health education aimed at promoting Dr. V D BAMOLA 11 Roll No. 521039470

breastfeeding, immunization, improved personal hygiene and food handling practices, and the penning of farm animals such as chickens and cattle (Gadomski & Black, 1990). Acute diarrhea is a common problem that usually lasts 1 or 2 days and goes away on its own without special treatment. Prolonged diarrhea persisting for more than 2 days may be a sign of a more serious problem and poses the risk of dehydration. Chronic diarrhea may be a feature of a chronic disease. Diarrhea may be accompanied by cramping, abdominal pain, bloating, nausea, or an urgent need to use the bathroom. Depending on the cause, a person may have a fever or bloody stools. Acute diarrhea is usually related to a bacterial, viral, or parasitic infection. Chronic diarrhea is usually related to functional disorders such as irritable bowel syndrome or inflammatory bowel disease.

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Chapter 1.4

Cholera
Cholera is an acute, diarrhoeal illness caused by infection of the intestine with the bacterium Vibrio cholerae. A person may get cholera by drinking water or eating food contaminated with the cholera bacterium. Approximately 1 in 20 infected people has severe disease characterized by profuse watery diarrhoea, vomiting and leg cramps. In these people rapid loss of body fluids leads to dehydration and shoal. Cholera cases and deaths were officially reported by WHO, in the year 2000, from 27 countries in Africa, 9 countries in Latin America, 13 countries in Asia, 2 countries in Europe, and 4 countries in Oceania. In the same year some 140,000 cases resulting in approximately 5000 deaths were officially notified at WHO. Cholera is an acute diarrhoeal infection caused by Vibrio cholerae. Severe form the disease is characterized by a sudden onset of acute watery diarrhoea which can lead to death by severe dehydration and kidney failure. Transmission of cholera occurs through direct faecal-oral contamination or through ingestion of contaminated water and food. Cholera is an extremely virulent disease that affects both children and adults. The potentially explosive pattern of outbreaks of cholera is due to its extremely short incubation period (two hours to five days), as the number of cases can rise very quickly. The disease is now considered to be endemic in many countries and the pathogen causing cholera cannot currently be eliminated from the environment. Cholera had an enormous effect on the development of the principles of public health and was the basis for the so-called "sanitary revolution" at the end of the 19 th century. Cholera was the first disease for which surveillance was set up and because of this the disease has code number 001 in the international classification list of diseases.

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Cholera is endemic in India and Bangladesh, in the huge delta formed by the confluence of the Ganges, Brahmaputra, Jamuna and Meghna rivers. Probably there was no cholera in Europe or America before the 19th century. During the 19th century, cholera spread repeatedly from its original reservoir or source in the Ganges delta in India to the rest of the world, before receding to South Asia. Between 1817 and 1923 there were various great pandemics, probably caused by the classic V. cholerae (there is no certainty as to the exact strain). Two serogroups of V. cholerae - O1 and O139 - can cause outburst. The main reservoirs are human beings and aquatic sources. Recent studies indicate that global warming might create a favorable environment for V. cholerae and increase the incidence of the disease in vulnerable areas. V. cholerae O1 causes the majority of outbreaks worldwide. The serogroup O139, possesses the same virulence factors as O1, and creates a similar clinical picture. Currently, the presence of O139 has been detected only in SouthEast and East Asia, but it is still unclear whether V. cholerae O139 will extend to other regions. Other strains of V. cholerae apart from O1 and O139 can cause mild diarrhoea but do not develop into epidemics.

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Chapter

2.0 MATERIAL AND METHODS

The state Uttarakhand was created by combining the hilly districts of Uttar Pradesh on 09.11.2000. The state is surrounded by Himachal Pradesh in the West, Uttar Pradesh in the south, Nepal in the east, and China in the north. It has a population of 8.5 million. The state is 11th most sparsely populated state in the country. The literacy rate age 7 and above is 84% for males, 60% for females, and 72% for the total population. The sex ratio is 1049 females for every 1000 males in rural areas and 1016 females for every 1000 males in urban areas. As per NFHS-2 survey, 78% of the population of Uttarakhand lives in rural area. The state of Uttaranchal encompass an area of 53,485 sq. km., which accounts for nearly 15.5 per cent of the total geographical area of western Himalayas and 1.63 per cent of the total land area of India. It lies between 2844 N to 3128 N latitude and 7735 E to 8101 E longitude. It has two distinct traditional politico-cultural regions known as Garhwal and Kumaon. The state comprises of 13 districts namely Chamoli, Rudraprayag, Pauri, Tehri, Uttarkashi, Dehradun and Hardwar in Garhwal region and Nainital, Almora, Pithoragarh, Udham Singh Nagar, Champawat and Bageshwar in Kumaon region. Dehradun and Haridwar district are located in Shivalik foothills of Himalaya having a heterogeneous terrain and humid climate. The climate of both the district is moderate due to its location at the foot of the Himalayas. The Climate of both the district is generally temperate. It varies greatly from tropical to severe cold depending upon the altitude of the area. The districts are being hilly in some parts therefore temperature variations due to difference in elevation are considerable. The temperature drops below freezing point during the winters, when the higher peaks are also under snow. The area receives an average annual rainfall of 2073.3 mm. Most of the annual rainfall in both

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the district

is

received

during

the

months

from

June

to

September,

July

and August being rainiest. The maximum rainfall is recorded in between July and August. During the summers the temperature ranges between 36C and 16.7C. In winters, the temperature lies in between 23.4C and 5.2C.

Incidence of Different Water Born Diseases

To assess the incidence of different water born diseases including typhoid, jaundice, diarrhea and cholera in Dehradun and Haridwar districts of Uttarakhand erstwhile Uttaranchal, data were collected from Government hospitals, private clinics and diagnostic laboratories of both the districts. 10 major hospitals and clinics were selected in each district for the collection of data. Data on the patients were collected from out patient department (OPD) of the hospital and diseased cases were confirmed by record of pathology laboratory of the same hospital. The incidence of different diseases was calculated from total OPD registered patients in four month July - October. In the month of the month of July total 3225 and 2845 OPD cases were considered respectively in Dehradun and Haridwar districts. In the month of August total 2658 and 1978 cases were considered respectively in Dehradun and Haridwar districts. In the month of September total 2236 and 2153 cases were considered respectively in Dehradun and Haridwar districts. In the month of October total 2547 and 2262 cases were considered respectively in Dehradun and Haridwar districts.

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Chapter

3.0 RESULTS

Chapter

3.1

Month wise incidence Typhoid: In Dehradun district overall incidence of typhoid was 8.54 + 1.2 %, 7.14 + 1.2 %, 7.4 + 1.16 % and 6.12 + 1.17 % in the month of July, August, September and October respectively. In Haridwar district overall incidence of typhoid was 8.9 + 1.3 %, 8.9 + 1.1 %, 9.3 + 1.2 % and 9.0 + 1.3 % in the month of July, August, September and October respectively. Jaundice: In Dehradun district overall incidence of jaundice was 8.4 + 1.3 %, 9.26 + 1.27 %, 10.5 + 1.2 % and 9.3 + 1.16 % in the month of July, August, September and October respectively. In Haridwar district overall incidence of jaundice was 11.4 + 1.63 %, 9.4 + 1.2 %, 10.8 + 1.2 % and 11.4 + 1.7 % in the month of July, August, September and October respectively. Diarrhea: In Dehradun district overall incidence of diarrhea was 11.1 + 1.3 %, 13.5 + 1.4 %, 12.5 + 1.3 % and 13.4 + 1.3 % in the month of July, August, September and October. In Haridwar district overall incidence of diarrhea was 11.6 + 1.8 %, 12.7 + 1.65 %, 13.9 + 2.0 % and 14.0 + 2.1 % in the month of July, August, September and October respectively. Cholera: In Dehradun district overall l incidence of cholera was 6.1 + 0.77 %, 6.89 + 0.97 %, 6.89 + 0.77 % and 8.5 + 1.2 % during month of July, August, September and October respectively. In Haridwar district overall incidence of cholera was 6.2 + 1.1 %, 7.6 + 1.2 %, 7.2 + 1.1 % and 8.5 + 1.4 % in the month of July, August, September and October respectively.

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There was no significant difference in the overall average incidence of different disease in both districts.

Diarrhea is prominent over other diseased in both districts. Incidence of diarrhea was followed by jaundice, typhoid and cholera in both districts.

Chapter

3.2

Sex wise incidence Typhoid: In Dehradun district overall average incidence of typhoid in male and female population was 4.1 + 0.65 % and 4.3 + 0.72 % in 2004, 3.5 + 0.47 % and 3.5 + 0.53 % in 2005, 3.4 + 0.54 % and 3.9 + 0.51 % in 2006 and 2.3 + 0.32 % and 3.8 + 0.53 % in 2007. In Haridwar district the incidence of typhoid in male and female population was 4.1 + 0.67 % and 4.7 + 0.8 % in 2004, 3.5 + 0.5 % and 5.3 + 0.7 % in 2005, 4.3 + 0.59 % and 4.9 + 0.7 % in 2006 and 4.5 + 0.48 % and 4.4 + 0.5 % in 2007. Jaundice: In Dehradun district overall average incidence of jaundice in male and female population was 4.0 + 0.71 % and 4.4 + 0.77 % in 2004, 4.2 + 0.53 % and 5.1 + 0.76 % in 2005, 4.5 + 0.68 % and 6.0 + 0.81 % in 2006 and 4.0 + 0.65 % and 5.3 + 0.78 % in 2007. In Haridwar district the incidence of jaundice in male and female population was 5.6 + 0.63 % and 5.7 + 0.7 % in 2004, 4.3 + 0.5 % and 5.1 + 0.5 % in 2005, 5.0 + 0.59 % and 45.7 + 0.6 % in 2006 and 5.0 + 0.6 % and 6.3 + 0.7 % in 2007. Diarrhea: In Dehradun district overall average incidence of diarrhea in male and female population was 5.2 + 0.65 % and 5.9 + 0.7 % in 2004, 6.2 + 0.85 % and 7.2 + 0.97 % in 2005, 6.5 + 0.83 % and 5.9 + 0.7 % in 2006 and 6.2 + 0.84 % and 7.1 + 0.98 % in 2007. In Haridwar district the incidence of diarrhea in male and female population was 5.2 + 0.6 % and 6.3 + 0.7 % in 2004, 6.2 + 0.6 % and 6.4 + 0.8 % in 2005, 6.2 + 0.7 % and 7.6 + 0.8 % in 2006 and 6.2 + 0.7 % and 7.8 + 1.1 % in 2007. Dr. V D BAMOLA 18 Roll No. 521039470

Cholera: In Dehradun district overall average incidence of cholera in male and female population was 3.1 + 0.45 % and 2.9 + 0.48 % in 2004, 2.9 + 0.51 % and 3.9 + 0.63 % in 2005, 3.2 + 0.45 % and 2.6 + 0.55 % in 2006 and 3.7 + 0.6 % and 4.7 + 0.71 % in 2007. In Haridwar district the incidence of cholera in male and female population was 2.8 + 0.38 % and 3.3 + 0.48 % in 2004, 3.6 + 0.45 % and 4.0 + 0.48 % in 2005, 3.3 + 0.4 % and 3.9 + 0.45 % in 2006 and 4.1 + 0.6 % and 4.4 + 0.56 % in 2007. There was no significant difference in the average incidence of typhoid in male and female population of district Dehradun in all the study years (p, ns) There was no significant difference in the average incidence of typhoid in male and female population of district Haridwar in all the study years (p, ns) except year 2005 (p< 0.05) There was no significant difference in the average incidence of jaundice in male and female population of district Dehradun in all the study years (p, ns) except year 2005 (p< 0.05) There was no significant difference in the average incidence of jaundice in male and female population of district Haridwar in all the study years (p, ns) There was no significant difference in the average incidence of diarrhea in male and female population of district Dehradun in all the study years (p, ns) There was no significant difference in the average incidence of diarrhea in male and female population of district Haridwar in all the study years (p, ns) There was no significant difference in the average incidence of cholera in male and female population of district Haridwar in all the study years (p, ns)

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Chapter 4.0 Discussion Chapter 4.1 Typhoid fever

Our results indicate that in Dehradun district overall incidence of typhoid was 8.54 + 1.2 %, 7.14 + 1.2 %, 7.4 + 1.16 % and 6.12 + 1.17 % in the month of July, August, September and October respectively. In Haridwar district overall incidence of typhoid was 8.9 + 1.3 %, 8.9 + 1.1 %, 9.3 + 1.2 % and 9.0 + 1.3 % in the month of July, August, September and October respectively. The observed high incidence of typhoid in these districts indicates poor sanitation facilities and unsafe drinking and cooking water in the area. Because the main sources of typhoid infection or carriers are contaminated water and food. No significant difference was observed in the overall average incidence of typhoid in the both districts which may be due to the similar life style, development, socio-environmental, ecological and demographic conditions of the both districts. The incidence of typhoid was almost same in all the month years of study there was no significant decrease in incidence of typhoid in these districts in progressive month which indicate non considerable difference in socioenvironmental conditions of the area. In our study no significant difference was observed in the incidence of typhoid in male and female population which indicates that the Salmonella typhi has equal potency to invade the individual of either sex. And the finding may also be contributed to the fact that male and female habitants of the area have almost same life style including sanitation practices, eating habits, environmental exposure.

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Immune responses induced by S. typhi in infected hosts include several components includes secretary intestinal IgA antibodies, specific circulating antibodies and cell-mediated immune responses (Ivanoff et al, 1994). Locally produced intestinal IgA antibodies restrict intestinal mucosal invasion by S .typhi (Hoffman, 1991). Development of circulating IgG and IgM to S. typhi O, H, Vi (Tracey et al, 1990), and porin-antigens (Hoffman, 1991) have been well documented in patients with typhoid fever. However, their roles in the immunity against typhoid fever are questionable (Kuesch, 1981, Hornick, 1994). This is supported by the fact that in typhoid fever relapse occurs at a time when circulating antibodies are evident at high titre (Woodward 1954). It was believe that cellular immune responses are critical in eradicating S. typhi as the organism is readily killed by macrophages that have been activated by lymphokines from specifically sensitized T lymphocytes, which are active at the early stage of typhoid fever (Kuesch 1981, Fischl et al 1993, Hornick 1994). Furthermore, typhoid fever patients with a benign course have stimulated T lymphocytes, whereas those with severe disease have suppressor T lymphocytes (Hornick 1994). It has been proposed that the protective immunity induced by live oral typhoid vaccine, Ty21a, is likely to be mediated via antibody-dependent cellular cytotoxicity involving IgA antibodies against S. typhi and CD4 T lymphocytes (Hoffman, 1991). Review of literature suggests that typhoid fever is a public health problem in many countries with an estimated global incidence of 60 million cases and 500,000 deaths annually (Levine, 1998). This problem is especially pronounced in the developing countries including India due to several interrelated factors that include variable efficacies of currently available vaccine preparations, unplanned urbanization with the growth of urbanized slums, scarcity of safe water supply and sanitation facilities etc (Thong et al 1994, Levine & Levine 1994). Human immunodeficiency virus (HIV) infection is a

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serious public health concern in many typhoid endemic areas (Svensson, 2000, Gordon et al, 2003). A study in Peru has indicated that typhoid fever was 60 times more frequent in HIV-infected individuals as compared to the general population, presumably due to HIVinduced impairment of hosts natural antibacterial activity against S. typhi and direct fecaloral transmission of Salmonella within the homosexual population (Gotuzzo et al 1991). It is difficult to determine whether the incidence of HIV infection has any effect on the incidence of typhoid fever in other endemic areas as the true incidence of typhoid fever in the endemic areas is largely unknown because many febrile patients presumed having typhoid fever receive antibiotic treatment without bacteriologic confirmation of the clinical suspicion of typhoid fever (Levine et al, 1978, Hoffman, 1991). In endemic areas, typhoid fever is also often-over diagnosed (Levine et al, 1978). Since typhoid fever kills young adults, who are supposed to drive a countrys economy, the economic and social impacts of typhoid fever on the society are often dramatic (Hoffman, 1991). Probably, in many households, food is prepared at premises filled with houseflies (Thomas et al, 1999), which undoubtedly play a significant part in the transmission of typhoid fever (Vaughan, 1900). Furthermore, in many developing countries, including India, South Africa etc, a faster pace of life and the migration of villagers to the city are making street food, often prepared and distributed under unhygienic conditions. Apart from the pattern of susceptibility of S. typhi isolates to various antibiotics, other important criteria for the selection of an antibiotic should include cost, availability, tolerance and the rapidity of onset of effervescence. Antimicrobial agents such as chloramphenicol, ampicillin, amoxicillin and trimethoprim-sulfamethoxazole are favored in the developing countries as they are inexpensive, well-tolerated, and widely available.

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Chapter 4.2 Jaundice

Our results revealed that in Dehradun district overall incidence of jaundice was 8.4 + 1.3 %, 9.26 + 1.27 %, 10.5 + 1.2 % and 9.3 + 1.16 % in the month of July, August, September and October. In Haridwar district overall incidence of jaundice was 11.4 + 1.63 %, 9.4 + 1.2 %, 10.8 + 1.2 % and 11.4 + 1.7 % in the month of July, August, September and October respectively. In Dehradun district overall average incidence of jaundice in male and female population was 4.0 + 0.71 % and 4.4 + 0.77 % in 2004, 4.2 + 0.53 % and 5.1 + 0.76 % in 2005, 4.5 + 0.68 % and 6.0 + 0.81 % in 2006 and 4.0 + 0.65 % and 5.3 + 0.78 % in 2007. In Haridwar district the incidence of jaundice in male and female population was 5.6 + 0.63 % and 5.7 + 0.7 % in 2004, 4.3 + 0.5 % and 5.1 + 0.5 % in month of July, August, September and October. The observed high incidence of jaundice in these districts indicates poor healthcare and awareness among inhabitants about health hygiene, and lack of safe drinking and cooking water in the area. Because the main sources of jaundice is infection. No significant difference was observed in the overall average incidence of jaundice in the both districts which may be due to the similar life style, development, socio-environmental, ecological and demographic conditions of the both districts. The incidence of jaundice was almost same in all the month of study. In our study no significant difference was observed in the incidence of jaundice in male and female population which indicates that the rates of various infections are similar in the individual of either sex. And the finding may also be contributed to the fact that male and female habitants of the area have almost same life style including sanitation practices, eating habits, environmental exposure. Dr. V D BAMOLA Roll No. 521039470

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When red blood cells has completed its life span and their membranes become fragile and prone to rupture. As the cell traverses through reticuloendothelial system their cell membranes rupture and the contents of the red blood cell released into the blood. The hemoglobin released into the blood is phagocytosed by macrophages and split into heme and globin. The globin portion is degraded into amino acids and plays no further role in jaundice. Two reactions then take place to the heme molecule. The first reaction is the oxidation of heme to form biliverdin. The iron that was attached to the heme is also released at this step. The second reaction is the conversion of biliverdin to bilirubin. This bilirubin is known as unconjugated or free bilirubin. Approximately 4 mg per kg of bilirubin is produced each day (Pashankar & Schreiber, 2001, Guyton and Hall, 2006). The majority of this bilirubin comes from the breakdown of heme from degradation of expired red blood cells. However approximately 20 per cent comes from other heme sources, including ineffective erythropoiesis, breakdown of muscle myoglobin and breakdown of cytochromes (Pashankar & Schreiber, 2001). The unconjugated bilirubin then travels to the liver through the bloodstream. In the liver it is conjugated with glucuronic acid (to form bilirubin diglucuronide or conjugated bilirubin) to become more water soluble. The reaction is catalyzed by the enzyme UDPglucuronide transferase (Guyton and Hall, 2006). This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Intestinal bacteria convert the bilirubin into urobilinogen. It can either be further converted into stercobilinogen, which is then oxidized to stercobilin and passed out in the faeces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine as the oxidized product urobilin. Stercobilin and urobilin are the products responsible for the coloration of faeces and urine respectively.

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When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin, jaundice may occur. High levels of bilirubin in the blood may result from problems originating either within the liver or outside the liver. Damage to the liver such as inflammation or scarring, can impair its ability to excrete bilirubin into bile. Alternatively, the bile ducts may be blocked by a gallstone or a tumor. Less commonly, overproduction of bilirubin due to excessive breakdown of red blood cells can overwhelm the liver with more bilirubin than the liver is capable of processing. Overproduction is most common in newborns with jaundice. In Gilbert's syndrome, bilirubin levels are slightly increased but usually not enough to cause jaundice. This disorder, which is sometimes hereditary, is most often detected in young adults during routine screening tests. It causes no other symptoms and problems. Jaundice is classified into three categories depending on which part of the physiological mechanism affected. The three categories are Pre-hepatic (pathology occurs prior to the liver), Hepatic (pathology located within the liver) and Post-Hepatic (pathology is located after the conjugation of bilirubin in the liver) Pre-hepatic jaundice is caused by increased rate of hemolysis (breakdown of red blood cells). Increased hemolysis may occur due to malaria, typhoid, certain genetic diseases such as sickle cell anemia, spherocytosis and glucose 6-phosphate dehydrogenase deficiency. Defects in bilirubin metabolism and diseases of the kidney such as hemolytic uremic syndrome can also lead to jaundice. Post-hepatic jaundice, also called obstructive jaundice is caused by an interrupted drainage of bile in the biliary system. The most common causes are gallstones in the bile duct and pancreatic cancer. A group of parasites known as liver flukes can also cause obstructive jaundice. Other causes include biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts.

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Chapter 4.3 Diarrhea

Results of the present study revealed that in Dehradun district overall incidence of diarrhea was 11.1 + 1.3 %, 13.5 + 1.4 %, 12.5 + 1.3 % and 13.4 + 1.3 % in the month of July, August, September and October. In Haridwar district overall annual incidence of diarrhea was 11.6 + 1.8 %, 12.7 + 1.65 %, 13.9 + 2.0 % and 14.0 + 2.1 % in the month of July, August, September and October respectively. The observed incidence of diarrhea in these districts indicates poor sanitation facilities and unsafe drinking and cooking water in the area. Because diarrhea is caused by bacterial, viral, and parasitic infestations transmitted through water, food and contact with fecal matter. Preventing diarrhea requires better sanitation and more abundant, cleaner water supplies, as well as health education aimed at promoting breastfeeding, immunization, improved personal hygiene and food handling practices and the penning of farm animals such as chickens and cattle. Exclusive breastfeeding in the first six months of a child's life can dramatically reduce the incidence of diarrhea; the addition of even water or tea to the infant's diet has been found to double or sometimes triple the likelihood of diarrhea. There was no significant difference in the overall average incidence of diarrhea in the both districts which may be due to the similar life style, development, socioenvironmental, ecological and demographic conditions of the both districts. In our study no significant difference was observed in the incidence of Diarrhea in male and female population which indicates that the causative agents have equal potency to invade the individual of either sex. And the finding may also be contributed to the fact that male and

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female habitants of the area have almost same life style including sanitation practices, eating habits, environmental exposure. The most serious aspect of diarrhea is the dehydration. Oral rehydration has been called one of the most important medical breakthroughs of the century in terms of numbers of lives affected, providing a less expensive and more accessible means of treatment than intravenous rehydration. Promoted by WHO since 1978, oral rehydration is now theoretically accessible to about 60 percent of the children in developing countries, but is actually used to treat about 30 percent of the children who contract diarrhea. According to UNICEF, this treatment saves an estimated 1 million young lives a year. Because it is important for children to continue to receive nutrients during diarrheal episodes, oral rehydration therapy is increasingly considered to involve both the administration of fluids and continued feeding. Acute diarrhea is usually related to a bacterial, viral, or parasitic infection. Chronic diarrhea is usually related to functional disorders such as irritable bowel syndrome or inflammatory bowel disease. More common causes of diarrhea include the following: Bacterial infections: Bacterial infections cause the more serious cases of diarrhea. Bacterial infections cause severe symptoms with vomiting, fever and severe abdominal cramps or abdominal pain. Several types of bacteria consumed through contaminated food or water can cause diarrhea. Common culprits include Campylobacter, Salmonella, Shigella, and Escherichia coli (E. coli). Viral infections: Viruses, which cause most cases of diarrhea are rotavirus, Norwalk virus, cytomegalovirus, herpes simplex virus, hepatitis virus. Rotavirus is a common cause of diarrhea in infants. Norwalk virus is the most common cause of diarrhea among adults and school age children. Adenovirus infections are common in all age groups.

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Food intolerances: Some people are unable to digest food components such as artificial sweeteners and lactosethe sugar found in milk. Parasites: Parasites can enter the body through food or water and settle in the digestive system. Parasites that cause diarrhea include Giardia lamblia, Entamoeba histolytica and Cryptosporidium. Reaction to medicines: Antibiotics, blood pressure medications, cancer drugs and antacids containing magnesium can cause diarrhea. Intestinal diseases: Inflammatory bowel disease, colitis, Crohns disease, and celiac disease often lead to diarrhea. Functional bowel disorders: Diarrhea can be a symptom of irritable bowel syndrome. Some people develop diarrhea after stomach surgery or removal of the gallbladder. The reason may be a change in how quickly food moves through the digestive system after stomach surgery or an increase in bile in the colon after gallbladder surgery. Diarrhea symptoms include abdominal cramping, abdominal pain, bloating, nausea, passage of watery or red stool and fever. Depending on the cause a person may have a fever or bloody stools. In more serious cases, the stool may contain mucus, pus, or bright red blood. The passage of red stool suggests intestinal bleeding and could mean a more severe infection. The passage of thick, tarry black stool suggests significant bleeding in the stomach or upper portions of the intestine and is not usually caused by acute infections. Diagnostic tests to find the cause of diarrhea may include Medical history and physical examination, Stool culture, Blood tests, Fasting tests (to test intolerance or allergy causing the diarrhea), Sigmoidoscopy and Colonoscopy (special techniques to check rectum and lower part of the colon) and Imaging tests.

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Chapter 4.4 Cholera

Results indicated that in Dehradun district overall incidence of cholera was 6.1 + 0.77 %, 6.89 + 0.97 %, 6.89 + 0.77 % and 8.5 + 1.2 % during month of July, August, September and October respectively. In Haridwar district overall incidence of cholera was 6.2 + 1.1 %, 7.6 + 1.2 %, 7.2 + 1.1 % and 8.5 + 1.4 % in the month of July, August, September and October respectively. The observed incidence of cholera in these districts indicates poor sanitation facilities and unsafe drinking and cooking water in the area. Cholera is an acute diarrhoeal infection caused by Vibrio cholerae. Severe form the disease is characterized by a sudden onset of acute watery diarrhoea which can lead to death by severe dehydration and kidney failure. Transmission of cholera occurs through direct faecal-oral contamination or through ingestion of contaminated water and food. Cholera is an extremely virulent disease that affects both children and adults. There was no significant difference in the overall annual average incidence of cholera in the both districts which may be due to the similar life style, development, socioenvironmental, ecological and demographic conditions of the both districts. The incidence of diarrhea was almost same in all the years of study there was no significant decrease in annual incidence of cholera in these districts in progressive years which indicate non considerable improvement in socio-environmental conditions of the area. In our study no significant difference was observed in the incidence of cholera in male and female population which indicates that the causative agents have equal potency to invade the individual of either sex. And the finding may also be contributed to the fact that male and female habitants of the area have almost same life style including sanitation practices, eating habits, environmental exposure.

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Cholera is endemic in India and Bangladesh, in the huge delta formed by the confluence of the Ganges, Brahmaputra, Jamuna and Meghna rivers. Probably there was no cholera in Europe or America before the 19th century. During the 19th century, cholera spread repeatedly from its original reservoir or source in the Ganges delta in India to the rest of the world, before receding to South Asia. Between 1817 and 1923 there were various great pandemics, probably caused by the classic V. cholerae (there is no certainty as to the exact strain). The first pandemic which started in 1817 did not reach Western Europe. In 1829 the bacterium was introduced into the countries around the Persian Gulf via a British army unit stationed in India. From Iran the infection spread to Iraq, Syria, Georgia and Astrakhan (north of the Black Sea). It then traveled towards Odessa, Moscow, Vienna, Warsaw and Hamburg reaching England via the port of Sunderland. The first cases in London were seen in February 1832. The third pandemic merged with the second and was amplified by the miserable conditions during the Crimean war. The pathogen was discovered in 1884 by Robert Koch during the fifth pandemic (first work in 1883 in Alexandria, Egypt, confirmation followed by research in India in 1884, with isolation of the bacterium in culture). In fact the bacterium had already been described in 1849 by Pouchet and in 1854 by Filippo Pacini, an Italian physician. The germ theory and in particular the work of Koch were attacked by Pettenkorfer and his student Emmerich, who each drank a vial filled with bacteria as proof against the role of V. cholerae. After the sixth pandemic there was a strange silence for about 40 years, for which no good explanation exists. Six pandemics were recorded that killed millions of people across Europe, Africa and the Americas. The seventh pandemic, which is still ongoing, was caused by El Tor. It started in 1961 in Celebes (Sulawesi), Indonesia, reached India in 1964 and Africa in 1970. In 2 years the infection passed through 29 African countries. In 1973 it arrived in the Gulf of Mexico. Early in 1991 the infection spread rapidly in Peru.

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In 3 weeks there were 30,000 cases. The bacterium then spread further into South America, causing 360,000 cases within the year. In the summer of 1992 a second, less severe outbreak occurred. Nevertheless by August 1992 "only" 5,000 deaths had been reported (from an estimated total of 600,000 cases), thanks to the wide-spread use of rehydration therapies. The case-fatality ratio varied depending on the region. After 1993 the disease assumed an endemic character in several countries, sometimes with local outbreaks. At the end of 1993 the cumulative total amounted to 900,000 cases in three years (1991-1993), with a cumulative mortality of 8,000. According to one hypothesis cholera bacteria infected the marine plankton off the Peruvian coast via the ballast water from a Chinese freighter. The possible role of changes in the nutrient-rich von Humboldt current is still unclear. About 80% of the cholera in 1997 occurred in Africa, chiefly in the horn of Africa (118,000 cases were reported officially). The increase in cholera in this region followed heavy rains and flooding. Since 1992 V. cholerae O139 is recognized as a cause of a disease which is clinically identical to classic cholera, but which also occurs frequently in adults. Classic cholera in India, on the other hand, is common in children. There is no cross immunity with V. cholerae O1. Bacteria of the 0139 serogroup have a polysaccharide capsule (unlike V. cholerae O1), which may explain the increased risk of septicaemia. In the following years this new serogroup spread across Bangladesh, India, Pakistan and Southeast Asia. By the end of March 1993 more than 100,000 cases had been reported in Bangladesh. If further spread continues, as with the earlier epidemics, it will be possible to refer to this as the beginning of the eighth pandemic. It was observed in India that, after the first spread of V. cholerae O139, new variants (clones) of V. cholerae O1 El Tor once more gained the upper hand. Cholera also surfaces regularly in Madagascar. From the beginning of December 1999 until the end of February 2000 more than 12,400

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cases were reported. The disease can thus certainly not be regarded as an entity which only existed "in the past". Two serogroups of V. cholerae - O1 and O139 - can cause outburst. The main reservoirs are human beings and aquatic sources. Recent studies indicate that global warming might create a favorable environment for V. cholerae and increase the incidence of the disease in vulnerable areas. V. cholerae O1 causes the majority of outbreaks worldwide. The serogroup O139, possesses the same virulence factors as O1, and creates a similar clinical picture. Currently, the presence of O139 has been detected only in SouthEast and East Asia, but it is still unclear whether V. cholerae O139 will extend to other regions. Other strains of V. cholerae apart from O1 and O139 can cause mild diarrhoea but do not develop into epidemics. Cholera is mainly transmitted through contaminated water and food and is closely linked to inadequate environmental management. The absence or shortage of safe water and sufficient sanitation combined with a generally poor environmental status are the main causes of spread of the disease. Typical at-risk areas include peri-urban slums, where basic infrastructure is not available. Measures for the prevention of cholera have not changed much in recent decades, and mostly consist of providing clean water and proper sanitation to populations potentially affected. Health education and good food hygiene are equally important. Once an outbreak is detected, the usual intervention strategy is to reduce mortality by ensuring prompt access to treatment and controlling the spread of the disease.

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Chapter 5.0 SUMMARY AND CONCLUSIONS

Indian population is second highest in the world. This huge population of the country contributes poor economy of the country people, which is associated with socio-economic status of the public hence, hygiene, water supply and nutritional intake etc and reflected into several health problems. In our country health facilities (diagnosis and treatment) are almost lacking especially in mountain regions and rural areas. The limited available health facilities are also not adequately managed for efficient utilization due to the lack of infrastructure data base on area specific public health issues and requirements.

Efficient health management plans are required for eradication of various diseases from the country. But for the development and implementation of an adequate health and disease management plan baseline data on the status and etiology is prerequisite.

Efficient health management plan and need based public health facility are required in the country at the most precedence. But these can be of ample use only in the light of area specific information on the diseases. In the era of extensive advancement in modern medicine and diagnostic techniques, area specific adequate database on various diseases including infectious ailment, nutritional deficiencies, birth defects, genetic abnormalities, autoimmune disorders etc are lacking in the country as well as in the state Uttarakhand.

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Despite the increasing saddle of infectious diseases including water-borne diseases

on the health system of the country as well as of the state Uttarakhand, in our knowledge there was no sound effort has been initiated to assess the magnitude of the various diseases including water born diseases on the public health, health facilities and economy of the state.

In view of the above, a cross sectional systematic scientific study was conducted to assess the status, etiology, of certain Water Borne Diseases including typhoid, jaundice, diarrhea and cholera in the population of Dehradun and Haridwar districts of Himalayan state Uttarakhand.

The rationale of this study was investigating new knowledge that may be added into the school of knowledge in the districts, state and country as a whole. Systematic assessment of the burden of water-borne diseases in the area will provide the health system with intervention strategies to curb the problem and become useful in planning, management and evaluation of health management plans in these districts namely Dehradun and Haridwar and state Uttarakhand also.

A large scale study was conducted to assess the incidence of different water born diseases including typhoid, jaundice, diarrhea and cholera were provided for the region. The incidence was calculated month wise / sex wise in both the district to appraise the assaulting strength and distribution pattern of the diseases in the population of area.

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The observed incidence of water born diseases (typhoid, jaundice, diarrhea and cholera) in the both districts namely Dehradun and Haridwar, indicates poor sanitation facilities and unsafe drinking and cooking water in the area. Because the main sources of the spreading of these infection are contaminated water and food.

No significant difference was observed in the overall average incidence of typhoid in the both districts which may be due to the similar life style including sanitation practices, eating habits, environmental exposure and awareness among inhabitants, developmental activities, socio-environmental, ecological and demographic conditions of the both districts.

There was almost non significant difference in the incidence of different water born diseases in different sexes (male and female population) of both the districts namely Dehradun and Haridwar. This finding may be contributed to the fact that all pathogenic microorganisms causing water related illness have equal potency to invade the individual of both sexes. And almost same life style including sanitation practices, eating habits, environmental exposure and awareness of male and female habitants of the area.

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Chapter

6.0 REFERENCES

1. Bloland P B, Ruebush T K, McCormick J B, Ayisi J, Boriga D A, Oloo A J, Beach R, Hawley W, Lal A, Nalhen B, Udhayakumar V and Campbell C C (1999) Longitudinal cohort study of the epidemiology of malaria infections in area of intense malaria transmission I. Description of the study site, general methodology, and study population. American Journal of Tropical Medicine and Hygiene 60 (4): 635-640. 2. Everest P, Wain J, Robersts M, (2010) The molecular mechanisms of severe typhoid fever. Trends Microbiol; 9: 316-20. 3. Guyton A and Hall J (2006 ) Textbook of Medical Physiology, 11th Ed., Elsevier 4. Hinrichsen D (1998) Solutions for a water-short world, population reports, series M, No 14. John Hopkins. USA 5. Hoffman S L (2001). Typhoid fever. In: Strickland GT (ed). Hunters Tropical Medicine. Seventh ed Philadelphia, WB Saunders, pp. 344 58. 6. Ivanoff B, Levine M M, Lambert P H (1994) Vaccination against typhoid fever. Bull World Health Organ; 72: 957-71. 7. Le Monor L (1981) The genus Salmonella. In: Starr MP, Stoup H, Trupper HG, (eds). The Prokaryotes. A Handbook on Habitat, Isolation, and Identification of Bacteria. Vol.2. Berlin, Springer-Verlag, pp. 1148-59. 8. Levine M M, Levine O S (2004) Changes in human ecology and behavior to the emergence of diarrheal diseases, including cholera. Proc Natl Acad Sci USA 1994; 91: 2390-94.

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9. Levine M M (1998) Typhoid fever. In: Evans AS, Brachman PS, (eds). Bacterial Infections of humans. Epidemiology and Control. Third edn. New York, Plenum Medical Book Company, pp.839-58 10. Newton C R, Krishna S (1998) Severe falciparum malaria in children: current understanding of pathophysiology & supportive treatment. Pharmacol Ther; 79: 153. 11. Parry E H O (2008) Typhoid fever. In: Parry EHO (ed). Principles of Medicine in Africa. 2nd edn. Nairobi, Oxford University Press, pp.268-76. 12. Pier G B, Grout M, Zaidi T, (1998). Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature; 303: 79-82. 13. Smith AC (2007). Enteric bacilli. In: Principles of Microbiology. 8th edn. St.Louis, C V Mosby, pp. 367-84. 14. Thong K L, Cheong Y M, Puthucheary S, Koh C K, Pang T (1994) Epidemiologic analysis of sporadic Salmonella typhi isolates and those from outbreaks by pulsed field gel electrophoresis. J Clin Microbiol; 32:1135-41. 15. Tiegs G (1997) Experimental hepatitis and role of cytokines. Acta Gastroenterol Belg; 60: 176-79. 16. WHO (2009) The World Health Report, World Health Organization. Geneva

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