John Hunwick

 

Internet marketing seems so simple in so many respects, but if it is so simple than why do so many people fail? One issue in Ghana is reliability of internet connections plus access to materials and advice for starting an internet business.

Education materials are readily available online for both internet marketing techniques and starting an internet marketing business, so some budding enrepreneurs in Accra are now competing in a global market. They do need additional advice.  The following extract is aimed at beginners:

When employed successfully Internet marketing techniques can be extremely effective, but without the proper know how they can be fruitless. There are a number of reasons that certain companies fail at successfully implementing an Internet marketing campaign. Knowing these reasons before you start your internet business and devise your Internet marketing strategy can be the difference between success and failure.

 

1. It is essential that when you affiliate yourself with people online you make sure they are on the up and up. Partnering yourself with someone who spams or violates other rules and regulations of the Internet can get you into a lot of trouble and also reflect negatively on your business.

 

2. Making the transactions with potential customers difficult is another reason many companies fail at Internet marketing. Sign-up for your website should be simple and quick, consumers do not want to have to provide an abundance of information to complete a transaction. Additionally, if a process seems too lengthy many consumers won’t complete it.

 

3. It is absolutely essential for any company that wishes to successfully market itself online to obtain e-mail addresses. Gaining a list of e-mails that you have permission to use gives you an invaluable resource for marketing to your target audience.

 

4. Never spam for any reason. Though it may be tempting to get your name out there quickly, spamming can get you banned from certain Internet service providers and that can hinder your ability to use e-mail as a legitimate marketing tactic in the future.

 

5. Always use viral marketing when it is possible. Not using viral marketing is like throwing free advertising dollars in the garbage. For more details visit to www.mrx-interview.com Viral marketing is no different from the various methods offline companies use to create buzz or advertise through word of mouth. When your customers are passing around your promotional material for you, it is free advertising and it is effective.

 

6. Instant gratification is a big desire among Internet users, so you should never make your customers wait. Make sure your website is fast, reliable and user-friendly. If you get traffic to your site, but people leave because they get frustrated waiting for your web page to load, getting the traffic there in the first place was pointless.

 

7. Marketing offline is just as important as marketing online. Even if you are creating a web based business, for more details visit to www.outsource-beginners.com it is important for you to reach people that don’t use the Internet regularly. Many companies fail to understand this concept, but even if you market offline with simple non-aggressive methods it is better than ignoring an entire demographic.

 

8. One of the biggest mistakes companies make when designing a website is not ensuring its compatibility with all users. Not everyone is technically savvy or running all the latest software. Your site should use flash, text and HTML so that anyone can use it .2. Search engines are a huge part of the Internet and it is absolutely essential to be listed with multiple search engine sites. Manually go to each search engine site and submit your URL to ensure that you are listed with them.

 

9. the most essential thing that any company can do to succeed at Internet marketing is to actively participate in their campaigns. Keep campaigns current, relevant to your business and make sure you are maximizing each campaigns potential. Then, sit back relax and have the patience that it takes to reap the benefits of a well-implemented Internet marketing campaign.

balwinder kaur
http://www.articlesbase.com/internet-marketing-articles/some-successful-ways-to-avoid-internet-marketing-708194.html

 

 

The most major part of internet marketing is probably the attempt at getting web traffic to a certain website.Traffic generally refers to the amount of hits and visitors a website receives. Traffic is also measured in quality based mostly on how targeted the potential customers are to the product. Local traffic are visitors who actually live in the location of the business being promoted.

Increasingly this is becoming a key way of promoting West African Businesses In the larger urbanisations.

For example, a website about fishing that sells fishing poles would want fishermen to visit more than someone who does not fish. There are many ways to generate traffic. Internet businesses can pay money to get traffic to their website using methods such as banner advertisements and pay-per-click campaigns. Other common methods of traffic generation include viral marketing and posting about your website on other websites.

Internet marketing is quite simply marketing that is done using the internet. Marketing refers to the promotion and advertisement of goods and services. It includes all the commercial aspects of transferring goods and services to a customer. Internet market usually includes advertising websites and products ordered over the internet, but internet marketing can also be used to promote offline businesses.

 

In addition to traffic, internet marketing also includes other aspects associated with getting the most customers to buy whatever the business is offering. These other aspects commonly include the effectiveness of the sales-pitch, the product, the website, and the customer service. The important parts of marketing differ from business to business, depending on what they are selling and to whom they are selling it.

 

Improving your internet marketing efforts will require that you analyze log files and tracking data. To do that, you must first install software on your website to record, log, and organize server data. This information will give you important statistics, such as how many people come to your website, which pages they visit, and how long they stay. You can use the information to compare the results of different campaigns. You can also use the information to find conversion rates. Once you find out when, where, and why some of your website visitors leave or do not leave your website, you can use that information to make changes that will help you get them to do what you want.

 

Internet marketers have to keep in mind certain concerns. For one, they have to worry about cost.The cost needs to be less than the revenue it generates, or else the internet marketing campaign will not be profitable. Another concern is traffic overload. If a website gets more traffic than it is used to getting, then it may overload the servers. That can make the servers slow or cause them to crash all-together. It’s recommended that marketers continually ensure that their servers can handle the traffic. A big marketing campaign can turn into a waste if the servers crash due to unusually high amounts of traffic.

 

When internet marketing, it is usually helpful to test and analyze. For example, testing different marketing campaigns will allow you to compare their cost-effectiveness. Also, testing how much of your computer resources are used in a marketing campaign will help you find out if they can handle a bigger campaign.

davinder ys
http://www.articlesbase.com/internet-marketing-articles/internet-marketing-internet-marketing-also-includes-other-aspects-associated-with-getting-the-most-customers-707572.html

 

 

So, you want to start an internet marketing business. Here are three things that you need before you begin the process.In Cape Town there are workshops on starting an internet marketing business and in web skills - including how to write a business plan.

Direction:
To succeed with an internet marketing business, or any business for that matter it is imperative that you have clear and concise direction in mind. 

 

Set goals. Where do you want to be in 3 months, 6 months, 1 year, 3 years, etc.? Commit these goals to paper and use them as a road map to success.

 

Develop the Right Product:

 

When creating a product or service you should ensure that it is something that you are passionate about. Do not jump into a niche just because you think it is profitable. Stick with something that you enjoy and are passionate about.

 

Understand:

 

If you are considering starting an internet marketing business to “get rich” overnight then you have been watching too many late night infomercials. There is no program or system that will make you an instant success in the internet marketplace.

 

Developing and operating a successful internet marketing business takes time, patience, and a very strong work ethic. Do not believe those who tell you that you can work part time and earn thousands of dollars per day as soon as you purchase their product.

 

Choosing the correct keywords is essential to the success of your online marketing campaign, it doesn’t matter whether its Google AdWords, Natural Search or even Article Marketing a keyword is a describing word or phrase for your product or service. For example you could use the keywords, Internet, Keywords, Marketing, Internet to describe this article.

 

The internet is an organized place and is adhering to certain standards. You can no longer upload a website and expect people to find it…..no one will find you! Just as an offline business has a Marketing Plan, an online business must have an Internet Marketing Plan. Once you’ve produced traffic to your site, you have to keep them interested, make the sale, and have them come back again. We are the experts, and are only job is to make your business successful.
Vebmarketing works hand in hand with you to analyze and bring out the qualities unique and special to your business.

Vipen Zizta.
http://www.articlesbase.com/business-articles/start-an-internet-marketing-business-is-growing-and-changing-along-with-the-internet-710026.html

 

 

Introduction

Adolescent parenthood often places the teen mother and her child at high risk for a variety of negative personal and social outcomes, one of which is an increased risk for abusive parenting (Schellenbach, Whitman and Borkowski, 1992). Adolescent mothers and their children are at a greater risk than children of adult mothers (Bolton, 2000).

Women under 20 years of age are more likely to experience maternal complication than women ages 20 and above (Eure, Lindsay and Graves, 2002; Zabin and Kiragu, 1998). Among 50 developing countries surveyed, an average of 23% of adolescent women, including both married and unmarried women, have given birth or are pregnant. Adolescent childbearing is most common in sub-Saharan Africa, at 25% of women ages 15 to 19. In the Central African Republic, Chad, Guinea, Madagascar, Mali and Niger, over one-third of adolescent women are pregnant or have had a child (Eure, Lindsay and Graves, 2002).

On average, among 16 surveys in Latin America and the Caribbean, 19% of all adolescent women have begun childbearing. The levels are highest in El-Salvador and Nicaragua, at 25%. In nine countries surveyed in Eastern Europe and Central Asia, about 8% of adolescent women are mothers.         

Most adolescents who are married or in a union have begun childbearing. In Latin America and the Caribbean, on average, 80% of married adolescents have begun childbearing, and in sub-Saharan Africa, 73%. Among all developing countries surveyed, South Africa has the lowest proportion of married adolescents who have begun bearing children, at 50%. Elsewhere, the highest level of childbearing among unmarried women ages 15 to 19 is in Nicaragua, at 10%, Nigeria, at 30%, and Ghana at 29% (Eure, Lindsay and Graves, 2002).

Predictors of higher incidence of adolescent childbearing among adolescent mothers have been examined in a variety of studies. Connelly and Strauss (1992) found that the mother’s age when her first child was born was a significant predictor of the occurrence of adolescent mothers. This relationship held even when other variables – such as income, race, education, number of children, and child’s age – were controlled. Bolton (2000) has pointed out that, there are numerous contextual similarities between adolescent parents and adolescent mothers – such as poverty, social isolation, and a poor understanding of child development – which may, collectively, provide the foundations for the development of parenthood.           

Both Belsky (1980, 1993) and Azar (2001) agree that adolescent childbearing is almost always multiply determined, with numerous factors interacting to contribute to the onset of abusive behaviour. Therefore, a risk assessment that measures different areas of risk simultaneously may provide a more comprehensive picture of the characteristics associated with adolescent childbearing among adolescent mothers than do assessments that do not combine multiple components. In the present study four contextual risk factors (social support, maternal psychological adjustment, maternal preparation for parenting and child temperament) were examined in combination as predictors of adolescent childbearing in adolescent mothers.

 

          Psychopathology or personality disturbances in one or both parents has frequently been implicated in the development of adolescent child bearing (Azar, 1991; Wupe, 1987). Most importantly, adolescent parents tend to have more psychological problems than adult mothers (Wurtz-Passino et al, 1993). Therefore, reconceptualizing parental psychological risk for adolescent mothers in terms of psychological adjustment and obtaining a more general assessment of psychological functioning may be more useful than trying to predict behaviour based on the diagnosis of specific clinical disorders.

 

          The importance of social support in the etiology of adolescent childbearing has also been identified (Azar, 2001; Belsky, 1980, 1993; Wolfe, 1985, 1987). Two common correlates of adolescent childbearing that reflect Belsky’s (1980) social support construct are the financial and emotional support available to the family. The socio-economic status (SES) of adolescent mothers and adult mothers frequently differs (Bolton, 2000). Lower SES of adolescent families are more highly represented in poor parenting. This over-representation may be due, in part, to the increased financial stress within families and the decreased availability of family-based financial resources to deal with unexpected expenses related to child care. The emotional support provided by the parents, peers, family, or spouse is also important in distinguishing adolescent mothers and adult mothers (Bolton, 2000; McKenny et al, 1991; Wolfe, 1987). Thus, both SES and emotional support are important aspects of social support reflecting the instrumental and interpersonal components important to a broad-based assessment of this construct.

 

          The third risk construct emphasizes the dysfunctional interaction patterns in adolescent childbearing. That is, a lack of knowledge of child development, unrealistic expectations, and a limited repertoire of skills for interacting with the child are predictive of adolescent child-bearing (Belsky, 1980; Bolton, 2000; de Lissovoy, 1973; McKenny et al, 1991; Schellenbach et al, 1992; Wolfe, 1985). In this way, a mother’s understanding and general expectations about her role as a parent, as well as her beliefs about how she is going to interact with her own child, may be early indicators of insufficient preparation for parenting, thus setting the stage for dysfunctional interaction with their children. This mental preparation for parenting termed cognitive readiness to parent by Borkowski and Colleagues (1992) – was found to be lower for teen than for adult mothers. Therefore, it is important to assess mothers’ preparation for parenting as a reflection of early predispositions towards dysfunctional parenting.

 

          Using the ideas from Wolfe’s (1987) theory, the two components of the psychological predisposition for aggression coping may mediate the relationship between the first four risk factors derived from Bolsky’s (1993) model – that is, social supports, maternal psychological adjustment, child temperament, and preparation for parenting – and the potential for adolescent childbearing. This mediational relationship may provide some understanding of the process through which maternal and early child factors increase the adolescent mother’s susceptibility to childbearing behaviours.

 

          Most research work on adolescent childbearing focused on the nature, causes, and prevalence. It is therefore, not to the knowledge of the researcher that studies linking adolescent childbearing and safe motherhood may have been conducted in Nigeria. It is against this background that this study becomes relevant in filling such missing gaps in our knowledge in the issue of adolescent childbearing and motherhood in Nigeria.    

 

Purpose of this Study

 

          The purpose of this research is to examine the predictive relationships between the contextual risk factors as social supports, maternal psychological adjustment, maternal preparation for parenting and child temperament serve to justify safe motherhood.

 

          In order to achieve the purpose of this research, the following research questions were answered at 0.05 alpha level.

 

1.           To what extent would adolescent childbearing attitudes (as social support, maternal psychological adjustment, maternal preparation for parenting and child temperament) when combined predict safe motherhood among adolescents of reproductive age in Abeokuta Metropolis of Ogun State, Nigeria?         

 

2.           What is the relative contribution of each of the factors to the prediction of safe motherhood among the adolescents?

 

Methodology

 

Research Design

 

          This study focused on adolescent childbearing factors as determinants of safe motherhood among adolescents of reproductive age in Abeokuta Metropolis of Ogun State, Nigeria. A descriptive survey research design was adopted in which questionnaire was employed in collecting data from the respondents on the variables involved in the study.

 

Participants

 

          The target participants for the study is made up all the Pre-degree female students of University of Agriculture, Abeokuta. A total of one thousand and two hundred (1200) female Pre-degree students were randomly drawn from the university Pre-degree female students to take part in the study. The range of participants’ age was between 16 years and 23 years with a mean age of 18.4 years and the standard deviation of 3.67.

 

Instrumentation

 

        Two instruments were used in the study.

 

(i)           Self-reporting Questionnaire on Adolescent Childbearing (SQAC) measures the social supports, maternal psychological adjustment, maternal preparation for parenting and child temperament. It has 25 items rated on a 4 point likert type scale. The respondents are to indicate their degree of agreement with each item by ticking Strongly Agreed (4); Agreed (3); Disagreed (2) and Strongly Disagreed (1). It has 0.64 and 0.69 as the internal consistency and revalidation reliability respectively.

 

(ii)          Motherhood Inventory (MI) measures the characteristics and values attached to the institution of motherhood. It has 20 items response format anchored on Partly True to very Untrue. The test-retest reliability of the inventory was found to be 0.66 and 0.71 respectively.

 

          All the two instruments were author-constructed and were considered valid through the favourable comments of experts in psychometrics on the suitability of the items.

 

Procedure for Data Collection

 

        The participants for the study were administered two questionnaires with the assistance of two research assistants and the University Guidance Counsellor. The collected questionnaires were scored and the data obtained from them were analysed to answer the research questions. On the whole, 1200 copies of the questionnaires were distributed and returned fully filled, giving a return rate of 100%.

 

Data Analysis

 

        The data collected were analysed using multiple regression and chi-square (X2) statistics to establish the relationship between adolescent childbearing and safe motherhood.

 

Results

 

        Results got from the data analysis are presented in Tables 1, 2 and 3.

 

Research Question 1:

 

        To what extent would adolescent childbearing factors when combined predict safe motherhood?

 

Table 1: Regression Analysis on Sample Data using A Combination of Independent Variables to Predict Safe Motherhood.

Multiple R:                 0.351

 

Multiple R-Square:     0.301

 

Standard Error:           3.37

Analysis of Variance

Sources of Variation

Df

SS

MS

F-Ratio

P-Value

Regression

3

5278.832

1759

5.10

<0.05

Residual

1196

517249.688

432.483

Total

1199

522528.512

                                                      

 

          Table 1 shows that the combination of the independent variables (social support, maternal psychological adjustment, maternal preparation for parenting and child temperament) in predicting safe motherhood among the adolescents yielded a coefficient of multiple regression (R) of 0.351, multiple correlation square (R2) of 0.301. The result shows that 30.1% of the variance in the prediction of safe motherhood is accounted for by the independent variables. The table also indicates that, the analysis of variance of the multiple regression data gave an F-ratio of 5.10 significant at 0.05 alpha level.

 

Research Question 2:

 

          What is the relative contribution of each of the factors to the prediction of safe motherhood among the adolescents?        

 

Table 2: Testing the Significance on Relative Contribution to the Prediction of Regression Weight of Independent Variables

S/N

Variables Description

Unstandardized Coefficients

Coefficients

Standardized

t-value

Sig.

B

Std Error

Beta

1

Social support

0.110

0.033

0.205

3.3

<0.05

2

Maternal psychological adjustment

0.124

0.037

0.288

3.3

<0.05

3

Maternal preparation for parenting

2.330

0.469

0.075

4.959

<0.05

4

Child temperament

0.144

0.044

0.022

1.2

NS

5

Constant

35.121

3.915

000

 

 

          Table 2 shows for each independent variable the standardized regression weight (B), the Standard Error Estimate (SEB), the Beta, the T-ratio, and the level at which the T-ratio, and the level at which the T-ratio is significant. As indicated in the table, the T-ratio associated with the four variables (social support, maternal psychological adjustment and maternal preparation for parenting) were significant at 0.05 alpha level. The contribution of child temperament can escalate threat and violence to the prediction of safe motherhood among adolescents of reproductive age. The degree of contribution of each of the variables in order of merit are: maternal preparation for parenting (B=2.330; t=4.959; p<0.05); social supports (B = 0.110; t = 3.3; P<0.05); maternal psychological adjustment (B = 0.124; t = 3.3; p<0.05); and child temperament (B = 0.144; t = 1.2; p>0.05).

 

Table 3: X2 Summary on Adolescent Childbearing Factors and Safe Motherhood. 

 

 

Variable Description

X2 Cal

Df

X2 tab

Sig (2 tailed)

1

Social support

16.986

3

7.81

0.001

2

Maternal psychological adjustment

29.762

3

7.01

0.000

3

Maternal preparation for parenting

33.956

3

7.81

0.000

4

Child temperament

5.969

3

7.81

0.113

* Significant at 0.05 alpha level

 

          The result on table 3 shows that each of the independent variables made significant contribution to the prediction on safe motherhood at 0.05 alpha level. This implies that there is a strong relationship between those factors and safe motherhood. The contributions of each of the variables shows that maternal preparation for parenting (X2 = 33. 956) has the most potent variable followed by maternal psychological adjustment, (X2 = 29.762); social supports (X2 = 16.986); and child temperament (X2 = 5.969) in that order.   

 

Discussion of Findings

 

        The major goal of this study was to find out the influence of adolescent childbearing factors as determinants of safe motherhood.

 

          It is on the above premise that the findings of the present investigation is reported. The result on Table 1 showed that adolescent childbearing factors either collectively or relatively predict safe motherhood. The joint combination of the four variables when taken together and regressed against safe motherhood account for 30.1% of the variance (R-square = 0.201). This is statistically significant as corroborated by the analysis of variance result of 5.10. This result agree with the findings reported by Bolton (2000); Eure, Lindsay and Graves (2002); Belsky (1980, 1993) and Azar (2001). This agreement was also supported by Wolfe (1987) and Belksky (1980).

 

          Maternal preparation for parenting was shown to significantly relate to safe motherhood. This result agrees with Borkowski and colleagues (1992). The result obtained in the study also showed that social support was a significant contributor to the prediction of safe motherhood. This finding supports the report of Bolton (2000); Azar (2001); Belsky (1980, 1993) and Wolfe (1985, 1987). Maternal psychological adjustment was considered significant in this study. This finding supports the work of Wolfe (1987) and Belsky (1980). Child temperament was not found to significantly predict safe motherhood. This result was however at variance from the work of Belsky (1980 and Wolfe (1987).

 

Conclusion and Recommendations

 

        Adolescent childbearing in any society of the world has been viewed as a social and health problem that requires urgent attention of well-meaning citizens. It is on this premise that the following recommendations are provided:

 

(i)           The government of Nigeria should as a matter of urgency adopt a National Adolescent Reproductive Health Policy.                   

 

(ii)          Youth centres be opened to provide information on family planning, reproductive and sexual health, and STIs and their treatment.

 

References

 

Azar, S.T. (1991). Models of child abuse: A metatheoretical analysis. Criminal Justice and Behaviour, 18, 30-46.

 

Azar, S.T. (2001). Child abuse and unrealistic expectations: Further validation of the parent opinion questionnaire. Journal of Consulting and Clinical Psychology, 54, 867-868.  

 

Belsky, J. (1980). Child maltreatment: An ecological approach. American Psychology, 35, 320-335.

 

Belsky, J. (1993). Etiology of child maltreatment: A developmental ecological analysis. Psychological Bulletin, 114, 413-434.

 

Bolton, F.G. (2000). “Normal” violence in the adult child relationship: A diathesis-stress approach to child maltreatment within the family. Family Abuse and Its Consequences (pp. 61-75). London: England Sage Publications.

 

Connelly, C.O. and Strauss, M.A. (1992). Mother’s age and risk for physical abuse. Child Abuse and Neglect, 16, 709-718.    

 

de Lissovey, V. (1973). Child care by adolescent parents. Children Today, 2, 22-25.       

 

Eure, C.N., Lindsay, M.K. and Graves, W.L. (2002). Risk of adverse pregnancy outcomes in young adolescent in an inner city hospital. American Journal of Obstetrics and Gynecology 186(5): 918-920.

 

McKenny, P.C., Kotch, J.B. and Broune, D.H. (1991). Correlates of dysfunctional parenting attitudes among low income adolescent mothers. Journal of Adolescent Research, 6, 212-234.

 

Schellenbach, C.J., Whitman, T.L. and Borkowski, J.G. (1992). Towards an integrative model of adolescent parenting. Human Development, 35, 81-99.

 

Wolfe, D.A. (1985). Child-abuse parents: An empirical review and analysis. Psychological Review, 97, 463-482.

 

Wolfe, D.A. (1987). Child abuse: Implication for child development and psychopathology (Vol. 10). Newbury Park, C.A.: Sage Publication. 

 

 

OLADEJI DAVID

 

Kora National Park is located in Coast province Tana River district about 280 kilometers from Nairobi. It was first gazetted as a reserve in 1973 and latter as a National Park in 1990.The park covers over 1787 Kilometers squared. The coastal region is mostly a tourist zone with large of it covered by National parks and reserves. It’s hot and humid all year with low rainfall.
Cold sea breeze sweeps through the land lowering the temperatures during the day. The temperatures usually range from 22-30 degrees all year.

It has seasonal rivers and has sloppy surfaces with rocky inselbergs .Its triangular in shape and an covered with dense woodland and scrubs.
Tana river whose source is Aberdare ranges passes on its northern boundary before it drains into the Indian Ocean.
The Kora National Park is on the north-east of Nairobi and is both accessible by road using the Thika- Mwingi highway getting through to the park by passing Kyuso a village on the North -East of Mwingi town or using an airstrip situated about Ten Kilometers East of the Park.

The Park has a good road network, making the  Kora National Park a suitable destination for rock climbing, fishing in Tana River, bird watching.
Other major attractions in the park include a walk in the wild, visiting Adamson’s Falls in Tana River, the Grand Falls and Kora rapids, visiting the George Adamson’s grave and many more.

Accommodation is never a problem at the coast province. Since its the hub of tourism activities, many accommodation facilities have been developed for budget, middle-class and high-end visitors.

Sullivan Pau

Authors:Bhurgri Ghulam Rasool,Momina Taki Muhammad,Shamim-Ur-Rehman,ShahMurad,RajKumar Chohan,DahriGhulam Mustafa, Shaikh zulfikar,

INTRODUCTION:

TUBERCULOSIS:

Tuberculosis, one of the oldest diseases known to affect human, is caused by bacteria belonging to mycobacterium tuberculosis complex. The disease usually affects the lungs, although in up to one third of cases other organs are involved. If properly treated, tuberculosis caused by drug susceptible strains is curable in virtually all cases. If untreated, the disease may be fatal within 5 years in more than half of cases. Transmission usually takes place through airborne spread of droplet nuclei produced by patients with infectious pulmonary tuberculosis (Mario C Raviglione, Richard JO Brein, 2003).

Tuberculosis is a disease of great antiquity. Today, tuberculosis gas become the most important communicable disease in the world, with over 8 millions cases of pulmonary tuberculosis occurring each year 95% which are in developing countries (A Gordon Leitch, 2000).

Tuberculosis is chronic granulomatous disease of human and other mammals caused by a group of closely related obligate pathogens, the mycobacterium tuberculosis complex, and comprising M. tuberculosis. The human tubercle bacillus - M. bovis - the bovine tubercle bacillus, -agricanum - a heterogeneous type found principally in effuational Africa with properties intermediate between the former two species and M-microti-a rare cause of disease involves and other small mammals but attenuated for humans. (PDO D awis et al, 2003).

Annual risk of infection

Areas

Current

Level

Annual decline

Trend (%)

Health resource

Availability

Industrialized

0.04-0.1

>10

Excellent

Middle income Latin America

West Asia

0.5-1.5

5-10

Good

Middle income East and South

Eest Asia

1.0-2.5

<5

Good

Sub-Saharan Africa

Indian Subcontinent

1.0-2.5

0-3

Poor

                                                                                                                                (A Gordon Leitch, 2000)

In 1994 World Health Organization (WHO) declared that tuberculosis (TB) constituted a global emergency. It developed a five point strategy known as direct observe treatment strategy (DOTS) in order to combat the increasing incidence of the disease. The main aim was to detect 70% of smear positive tuberculosis (TB) cases and to treat85% of smear positive new cases successfully. This strategy has improved worldwide cure rates. Tuberculosis is an increasingly important cause of morbidity and mortality in refugees and displaced populations, particularly during the post acute phase of complex emergencies (Alison H Rodger et al., 2002).

EPIDEMIOLOGY:

In Pakistan, only limited data is available, however, the prevalence of tuberculosis is estimated to be as high as 250,000 cases annually. According to official estimates, the rate of open bacillary cases among adult population (15 years and above), was 17% and among children 5 to 9 years of age, 13% were infected with tuberculosis. It is thought to be the fourth major cause of all deaths in Pakistan (Shamim A Qazi et al., 1998).

PATHOLOGY OF TUBERCULOSIS:

CASE WITH INFECTOUS TUBERCULOSIS

Cough and generate droplet nuclei which are ingaled by a contact

Primary

Onset of CMI response

Bacillimia                                                   Apical Implant

Sterilization of the primary complex

Immunosuppressive event

Multiple of tubercle bacilli

Restoration of CMI

Caseation of necrosis

        Infectous tuberculosis

Figure: Schematic representation of the basic events in the pathogenesis of tuberculosis.

CMI: Cell mediated immune.

(VB Balasurbramanian et al., 1994).

DRUG TREATMENT OF TUBERCULOSIS

Tuberculosis is among the top ten cause of global mortality and affects low icome countries in particular. The treatment of smear positive tuberculosis using World Health Organizzation (WHO) directly  observed treatment, short course, Direct observe treatment strategy (DOTS) has far highest impact while BC immunization recuces childhood tuberculosis mortality (Martien W Borgdorff et al.m 2002).

Drugs used in the treatment of tuberculosis can be divided into two major categories. First line after combined the greatest level of efficacy with unacceptable degree of toxicity. These include isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide. Excellent results for patients with non drug resistant tuberculosis can be treated with 6 month course of treatment, for the first 2 months, isoniazid, rifampin and pyrazinamide are given, followed by isoniazid and rifampin for remaining 4 months (William A Petri Jr, 2001).

RIFAMPIN

Rifampin is a semisynthetic broad spectrum bactericidal antibiotic derived from streptomyces mediaterani.The introduction of this antibiotic that permitted the development of the first effective short course of 9 month chemotherapy for tuberculosis.

It is an addition of antituberculosis activity, it has wide range of activity against other bacteria including staphylococcus, Streptococcus, Clostridium, Coliforms, Pseudomonas, Proteus,Shigella and Legionella. Rifampin is almost completely absorbed from gastrointestinal tract after an oral dose. When it is taken is an empty stomach the plasma levels of 6-7 ug/ml are reached at 3 hours and its half-life of about 5 hours (A Gordon Leitch, 2000).

Adverse effects:

Rifampin dependent antibodies are considered responsible for most of immunological side effects in which hepatotoxicity, thrombocytopenia and allergic reactions are important (Mehta YS et al., 1996). Rifampin causes anorexia, nausea, vomiting, diarrhea, fever, dizziness, bone pain, shortness of breath, urine and saliva are colored orange red (Cheema MA, 2000).

ISONIAZID

Since its  introduction in 1952 isoniazid has been widely recognized as a safe and effective chemotherapeutic agent against tuberculosis. Numerous studies of isoniazid in combination with other tuberculous drugs have repeatedly demonstrated its therapeutic efficacy (Richard et al.,1972).

Isoniazid is the most widely used antituberculosis agent. It is an ideal in many aspects, being bactericidal, relatively non-toxic easily administered and inexpensive. It is readily absorbed from the gastrointestinal tract, with peak concentration of approximately 5ug/ml occurring about 2 hour after administration. It penetrates to all tissues including cerebrospinal fluids (C.S.F.) some part of drug excreted in urine in unchanged form but proportion is acetylated by hepatic acetyl transferase to an inactive form. Drug is usually given orally with combination of rifampin and pyrazinamide are available (A Gordon Leitch, 2000). Isoniazid is still most important drug world wide for the treatment of all types of tuberculosis. The commonly usual dose is 10-50 mg/kg/day with maximum of 300 mg (William A Petri Jr, 2001).

The incidence of adverse effects of isoniazid are skin rash, fever , jaundice hypersensitivity to isoniazid may result in fever, various skin eruption occurs (William A Petri Jr, 2001).

Isoniazid preventive therapy is contraindicated in persons with chronic active hepatitis should be given caution to person who consumes alcohol daily (M Suess, 1994).

ETHAMBUTOL

Ethambutol is a synthetic, water soluble, heat stable compound. Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol. Ethambutol is an ingibitor of mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosy1 transferases are involved in the polymerization reaction of arbinoglycan, an essential component of the mycobacterial cell wall (Henry FC, 2001). It is rapidly absorbed from intestine. It is excreted in urine. It should not be given in renal disease (MA Cheema, 2000). The most important side effect is optic neuritis, resulting decrease of visual acuity and loss of ability to differentiate red from green (William A Petri Jr, 2001).

Hypersensitivity to ethambutol is rare. The most common serious adverse event is retrobulbar neuritis causing loss of visual acuity and red green color blindness. The dose related side effect is more likely to occur at a dosage of 25 mg/kg/day continued for several months. The peripheral neuropathy owing to demyelinization. Other less common adverse effects include gastrointestinal intolerance, hyperurecemia, and hypersensitivity reactions including rash, and rarely thrombocytopenia. It is safe during pregnancy with no known teratological effects (Edwards D,Chan,2003).

PYRAZINAMIDE

Pyrazinamide is bactericidal in an acid environment and as sterilizing effect on intracellular mycobacteria. It is well absorbed from gastrointestinal tract, with peak concentration of about 50ug/mloccurring 1.5-2 gour after ingestion. It penetrates well into tissues including cerebrospinal fluid (A Gordon Leitch, 2000).

Pyrazinamide is synthetic orally effective bactericidal ant tubercular agent used along with isoniazid and rifampin (William A Petri Jr, 2001).

The reasons for this increased incidence of hepatotoxicity reactions in developing countries are unclear, Perhaps poor nutrition, increased age, wide spread parasitism, chronic infections, indiscriminate use of various drugs without prescription may play a role individually or collectively (H Turktas et al.,1994).

Gastrointestinal reactions, cutaneous reactions, sidiroblastic anemia (A Harries, 2003). Moreover pyrazinamide is considered to be significantly less hepatotoxic than isoniazid and rifampin. Less common adverse reactions to pyrazinamide include rhabdomyolysis with myoglobinuric renal failure, gouty arthritis, photosensitivity, maculopapular raxh, thrombocytopenia, increased serum iron, urticaria, and other hypersinsitivity reactions (Edward DE Ehan et al., 2004).

STREPTOMYCIN

Streptomycin is tuberculocidal, but less effective than isoniazid or rifampin, acts only on extracellular bacilli (because of poor penetration into cells). Thus, host defense mechanisms are needed to eradicate the disease. It penetrates tubercular cavities, but does not cross to the cerebrospinal fluid (CSF), and has poor action in acidic medium. Resistance developed rapidly when streptomycin was used alone in tuberculosis most patients had a relapse (Tripathi, 2003). Streptomycin is bactericidal for tubercle bacillus in vitro. Concentration as low as 0.4 mg/ml may inhibit the growth. Vast majority of strains of mycobacterium tuberculosis are sensitive to 10mg/ml (William A Petri Jr, 2001)

Untoward effects include rash and fever, auditory and vestibular function of eighth cranial nerve is affected (William A Petri Jr, 2001).

BCG

Unfortunately, the protective efficacy of BCG, the most widely used vaccine against pulmonary tuberculosis varies from 0% to 80%. BCG gives good protection (75-80%) against disseminated tuberculosis includes tuberculous meningitis, in childhood, BCG is given at birth or as soon as possible, therefore after and although the duration of protection is uncertain, it may not be longer than 15 years, this limiting protection against infectious pulmonary tuberculosis, which may occur mainly in adults (Martein W Borgdorff et al., 2002).

Today over, 70 years of BCG development, it is still the only tuberculosis vaccine availed, and the achievements of tuberculosis vaccine research have been largely operational, such as expanding delivery of BCG through the expanded programe on immunization and holding field trials in different geographical locations (Ann M Ginberg,2002).

MATERIAL AND METHODS

This study was carried out in the department of Pharmacology and Therapeutics, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre, Karachi, from January 2005 to June 2005.

The 100 newly diagnosed patients of pulmonary tuberculosis, enrolled is this study after taking informed and written consent.

The patients were selected as diagnosed cases of pulmonary tuberculosis from medical chest OPD and chest ward of Jinnah Postgraduate Medical Center, Karachi. Out of these 97 patients were associated through out the study period. Out of remaining three have not come for follow up.

                                     

All patients, in this study, were selected according to following criteria:

INCLUSION CRITERIA:

• Diagnosed cases of pulmonary tuberculosis.
• Age between 2o to 70 years.
• Sex either male or female.

EXCLUSION CRITERIA:

• Patients suffering from liver disease.
• Patients suffering from cardiac disease.
• Patients suffering from renal disease.
• Patients suffering from diabetes mellitus.
• Patients suffering from other respiratory disease.
• Patients suffering from HIV infections.
• Pregnant or nursing women.
• Patients with previous multiple drug resistance.

The study period extended up to 24 weeks and 12 follow up visits of patients were taken. The required information such as name, age, sex, occupation, address, details of follow up visits and laboratory investigations etc, of each patients were recorded on proforma especially designed for this study.

The selected patients were divided according to untoward effects of drugs during study period.

Group1:                 In this group those patients were included who manifested the hepatitis in different age groups

Group2:                 In this group those patients were included who manifested the peripheral neuropathy inh defferent age groups

Group3:                 In this group those patients were included who manifested the skin rashes in different age groups

Group4:                 In this group those patients were included who manifested the joint pain in different age group

Group5:                 In this group those patients were included who manifested the optic neuritis in different age group

Group6:                 In this group those patients were included who manifested the thrombocytopenia in different age group

Group7:                 In this group those patients were included who manifested the nephrotoxicity in different age group

Group 8:                In this group those patients were included who manifested the ototoxicity in different age group

MATERIALS

• Isoniazid—adult 5 mg/kg -maximum 300 mg
• Rifampin—-adult 10 mg/kg -maximum 450 mg
• pyrazinamide 15-30 mg/kg
• Ethambutol 15-25 mg/kg-maximum 300 mg
• Streptomycin — 15 mg/kg - maximum 1 gm
• Disposable syringes.
• C.P. bottles.
• Kits for the liver function test, measurement of urea, creatinine

Ninety seven patients were studied after medications with anti tuberculosis therapy and divided in eight groups after the manifestation of untoward effects of therapy.

The observations of all the treatment groups were recorded on day 0, day 30 and day 80.

Table 1 and figure 1 show hepatitis after taking the anti tuberculosis drugs. The hepatitis was manifested more in combined therapy during medication of pulmonary tuberculosis. The hepatitis found significant different with p < 0.01 among anti tuberculosis therapy. Out of 97 patients, there were 15 patients were affected by this untoward effect. The highest proportion of hepatitis in isoniazid (10.3%) followed by pyrazinamide (3.1%) and rifampin (2.1%

 The hepatitis in different age groups. The decade between 20-29 of age has shown maximum number of hepatitis (5.1 & followed by the extreme age 60-69 years (P<0.05), keeping the high proportion of isoniazid as compared to pyrazinamice (1.03%) and rifampin (2.06%) in different age groups. Isoniazid manifested 4 cases of hepatitis in age group 20-29 years, pyrazinamide 1 respectively. Four patients produced hepatitis in age between 60 to 69. Pyrazinamide produced hepatitis in age between 60 to 69. Pyrazinamide produced hepatitis (2.66%). INH and rifampin affected with equal percentage (1.03%). Two patients were produced hepatitis in age between 30-39 years. The INH and rifampin affected with equal (1.03%) in this age group respectively. It was non significant statistically. One patient was affected by isoniazid in the age group of 50-59 years. It was non significant statistically

 The peripheral neuropathy in 25 patients out of 97 patients. The isoniazid produced more peripheral neuropathy than other causative drugs. The isoniazid affected 11.3% patients. The pyrazinamide and ethambutol produced the peripheral neuropathy in same percentage (7.2%). It was non significant statistically.

The peripheral neuropathy in different age groups. The age between 60 and above was more affected than other age groups. Isoniazid produced 602% peripheral neuropathy in this age group. Ethambutol produced 1.03% peripheral neuropathy. The age group between 20-29 developed peripheral neuropathy by isoniazid 301%, pyrazinamide 2.01% and ethambutol 1.03% respectively. The total patients were 6 with this age group. The age between 30-39 manifested peripheral neuropathy by isoniazid 1.03% and ethambutol 1.03% respectively. The age between 40-49 was affected by peripheral neuropathy by pyrazinamide 3.1% and ethambutol 3.1%                                                                                                  

Therapy produced, 3 patients, thrombocytopenia. The rifampin produced thrombocytopenia in 3.1% males.

 Thrombocytopenia according to age groups. The combined therapy affected in age between 40-49, 1.03%, 50-59, 1.03% and 60 and above 1.03% respectively. The rifampin produced this side effects with same percentages i.e. 1.03% in age groups 40-49, 50-59 and above.

            Table 10 and figure 10 show the joint pain as an adverse effect of anti tuberculosis drugs. The combined therapy affected 8 patients out of 97. pyrazinamide produced joint pain in 8.24% patients.

Table 12 and figure 12 show the joint pain according to age groups. The pyrazinamide affected 3.09% in age between 60 and above, 2.06% in age between 20-29 and 1.03% in further age groups respectively.

 The optic neuritis. The combined therapy produced optic neuritis in 7 patients out of 97. ethambutol produced 7.2% optic neuritis

 The optic neuritis according to age groups. The combined therapy produced the optic neuritis in 3 in 6o to69, 2 in 50-59 and one in 30-39 and 40-49 years respectively. The ethambutol produced the optic neuritis in 3.09 in age between 60-69, 2.06% in 50-59 and 1.03% in 40-49 and 30-39 tears.

 Skin rashes as an adverse effect of anti tuberculosis drugs. The skin rashes found significant (P<0.01) by combined therapy. The combined therapy produced skin rashes in 6 patients out of 91 patients. The pyrazinamide produced skin rashes (4.12%) and rifampin produced 2.1% respectively.

Skin rashes in age groups. The combined therapy produced skin rashes in 2 from 20-29 years age group, 1 from 40-49 years, 1 from 60-69 respectively. The pyrazinamide produced skin rashes 2.06% in age between 20-29 years, 1.03% in 50-59 years, 1.03% in 60-69 years age group, 1.03% in 50-59 years respective

 Nephrotoicity as an adverse effect. Streptocomycin was main drug to manifest the nephrotoxicity in combined therapy during treatment of pulmonary tuberculosis in combined therapy during treatment of pulmonary tuberculosis patients. Out 97 patients, there were 3 reactions documented in this study.   Nephrotoxicity in gender after taking the anti tuberculosis drugs. Two males and one female was affected during the study

The nephrotoxicity in different age group. In the age group 30-39 1, 40-49 1, and 50-59 1 reaction was documented in this study.

 The ototoxicity after taking anti tuberculosis drugs. There were 2 reactions recorded in this study.

Adverse effect

Pyrazinamide

Isoniazid

Ethambutol

Rifampin

Streptomycin

Total

%

95% CI

Peripheral neuropathy

7 (7.2%)

11 (11.3%)

7 (7.2%)

-

-

25

25.8

17.80-35.1

Hepatitis

3 (3.1%)

10 (10.3%)

-

2 (2.1%)

-

15

15.5

9.2-23.7

Joint pain

8 (8.2%)

-

-

-

-

8

8.20

3.9-15.0

Optic neuritis

-

-

7 (7.2%)

-

-

7

7.20

3.2-13.7

Skin rashes

4 (4.2%)

-

-

2 (2.1%)

-

6

6.20

2.5-12.4

Table show overall side effects of ATT in this study.

FIGURES:

Overall Frequency of Adverse Effect

(n=69)

DISCUSSION:

This study observed the untoward the untoward effects of antituberculous drugs in pulmonary tuberculosis patients. The selected patients were divided into two groups according to the age and sex. In this study the following reaction i.e., hepatitis, peripheral neuropathy, thrombocytopenia, joint pain, optic neuritis, ototoxicity and nephrotoxicity were recorded in the first line antituberculous drugs used in pulmonary tuberculosis patients.

The adverse effects of antituberculous drugs i.e., isoniazid (INH), pyrazinamide, rifampin, ethambutol and streptomycin were observed during this study, discussed here.

Isoniazid (INH) 300 mg per day was started in selected 97 tuberculosis patients. The major side effects were recorded after two weeks of medication, which included hepatitis and peripheral neuropathy.

Hepatitis – there were 10 reactions of hepatitis were documented in this study. In a group of gender, there were 7 reactions in male and 3 reactions in female. According to age group between 20-29, the isoniazid produced 4 reactions, 3 reactions in 40-49, 1 reaction in other age groups. Isoniazid was stopped but remaining other drugs rifampin, pyrazinamide, ethambutol and streptomycin were continued in these patients.

After the stoppage of isoniazid, the liver function test was normal in 6 cases, isoniazid was reintroduced after 2-3 weeks with dose of 50 mg per day and was increased subsequently to 300 mg per day. There were 4 cases referred to the Medical Outpatient Department (OPD) for management of liver disease.

Peripheral neuropathy – isoniazid produced 11 reactions of  peripheral neuropathy out of 25 reactions in this study. According to gender, 4 reactions were produced in male and 7 reactions in female. According to age group the peripheral neuropathy produced in age group 30-39 and 40-49 respectively. This showed the higher side effect of isoniazid in older age group.

Pyrazinamide (1-2 g/day) – the major side effect of this drug were produced after 3-4 weeks of medication. The hepatitis 3, peripheral neuropathy 7, joint pain 8, and skin rashes were documented in this study.

Hepatitis – the pyrazinamide produced 3 reactions of hepatitis in this study. According to gender, 1 male and 2 female reactions were recorded in this study. According to age, pyrazinamide produced 2 reactions in age group of 60-69 and 1 reaction 20-29 of age group. The 1 reaction of pyrazinamide was subsided when drug was stopped. But 2 reactions in older age group, the liver function test did improved and they were referred to the Medical Outpatient Department (OPD) for the management of liver disease.

Peripheral neuropathy – there were 7 reactions caused by pyrazinamide were documented in this study, according to gender, 2 reactions in male and 5 reactions in female according to age group, age between 50-59 3 reactions and 1 reaction in age group 20-29 and 40-49 respectively. These reactions were reversible after decreasing dose of pyrazinamide.

Skin rashes – the pyrazinamide produced 4 reactions out of 6 reactions of antituberculous drugs in this study. According to gender, in female 3 reactions and 1 reaction in male were recorded in this study. According to age group, 2 reactions were recorded in age group of 20-29 and 1 reaction in 50-59, 60-69 respectively. Skin rashes were subsided after stoppage of pyrazinamide for 3 weeks.

Joint Pain – there were 8 reactions of joint pain documented in this study. This study showed that pyrazinamide was only causative drug for joint involvement, the uric acid level was done before and after the start of drug. A remarkable increase level of uric acid was noted after the pyrazinamide treatment. Thus the drug was stopped in these 8 patients and later the level of uric acid significantly decreased and joint involvement clinically improve.

                Ethambutol was administered at dose of 15-30 mg/Kg/Day. The side effects of this drug were manifested after 2-3 weeks of treatment. The peripheral neuropathy and optic neuritis were recorded as main side effects.

Peripheral neuropathy – there were 7 reactions of peripheral neuropathy recorded in this study. The ethambutol produced these reactions in 2-4 weeks after starting of treatment. According to gender, 5 in female and 2 reactions in male, were observed in this study. According to age group, 3 reactions in 50-59 and 1 reaction in each age group respectively. These reactions were reversible after stoppage of the drug.

Optic neuritis – the ethambutol produced the 7 side effects of optic neuritis in this study. According to gender, male manifested 4 and female 3 reactions of optic neuritis in this study. According to age group 3 reactions in 60-69 age group and 2 in 50-59 group and 1 reaction in 50-59, 30-39 age group respectively in this study. Drug was discontinued in these 7 cases of optic neuritis but the remaining four other drugs were continued. They were referred to Eye Outpatient Department for the management of optic neuritis. Only in two patients drug was reintroduced with low dose 15-20 mg/Kg/Day.

Rifampin (450 mg/day) – after 2-3 weeks of starting with combined therapy, the major side effects were manifested. When this drug was hold, the hepatitis 2 and skin rashes 3 were improved and reactions of thrombocytopenia were documented in this study.

Hepatitis – according to gender, 1 reaction of hepatitis in male and 1 in female produced by rifampin. According to age group, 1 reaction in 30-39 and 60-69 were produced by rifampin. One side effect of hepatitis was improved when drug was stopped after one week and other patient was referred to Medical out patient department for further management.

                Skin Rashes – the rifampin developed the skin rashes in two patients; one in male and one in female in this study. According to age group, 1 adverse effect in 40-49 and 50-59 were observed respectively. These skin rashes were reversible after stoppage of drug.

Thrombocytopenia – after 5-11 weeks of treatment of tuberculosis patients, the level of platelets were decreased and clinically the patients were complaint epistaxis, bruises, and petechial rashes. Rifampin was stopped in 3 patients but the remaining other four drugs were continued.

Streptomycin (1 g per day) – it was started with other drugs. After 3-7 weeks of medication, 3 patients complaint of oliguria and 2 patients presented during follow up with hearing deficit. These reactions proved clinically and laboratory investigations.

Nephrotoxicity was recorded in these patients two in male and 1 in female. According to age group 1 in 30-39, 2 40-49 and 1 50-59 side effects were documented in this study. Drug was stopped for 3 weeks and found that blood urea nitrogen and creatinine levels were decreased, therefore this drug was permanently stopped and the remaining four drugs were continued.

The proximal renal tubule cells may accumulate aminoglycoside, accounting for nephrotoxicity associated with aminoglycosides. The mechanism of renal toxicity is hypothesized to by the inhibition of intracellular phospholipase in the proximal tubule. The renal insufficiency is typically characterized by the nonoligouric decrease in glomerular filtrate rate occurring after at least taking a week therapy. Baseline and periodic surveillance of analysis blood urea nitrogen levels, creatinine values is indicated (Edward et al., 2004).

Streptomycin is nephrotoxic and should used with caution in patients with renal impairment. If reaction is trouble some which is an infrequent occurrence, the dose may be reduced (NCG,2002).

Ototoxicity – there were 2 reactions recorded in this study. According to gender, 1reaction was in male and 1 in female was documented in this study. Side effects of streptomycin were recorded. One in age group 20-29 and one in 40-49. The drug was a stopped and patients were advised to consult in Ear Nose and Throat OPD. Remaining other drugs were continued.

Interestingly, the damage may be fairly isolated to either the choclear or vestibular component, or rarely both. The mechanism for the cochlear toxicity is unclear, although the target site is considered to the outer hair cells of the organ of corti.

Aminoglycoside induced cochlear dysfunction is generally considered to be irreversible. Injury to the hair cells of the ampullar cristae by aminoglycosides is the mechanism of the vestibular toxicity. Sign and symptoms of vestibular toxicity include nausea, vomiting, vertigo and nystagmus (Edward et al., 2004).

Our study matches with study of Menzies et al (2005), who observed the side effects of antituberculous therapy. They reported that at least monthly a nurse, a case manager, a treating physician saw the 430 test patients who had active tuberculosis therapy . At the time of their visit patients were questioned specifically about the occurrence of common side effects of their tuberculosis drugs. Liver enzyme levels were checked routinely in all patients after one month of treatment. Patients were encouraged to return at any time if symptoms or problems arose during therapy.

The striking observation is that pyrazinamide was association with rate of toxicity that was threefold higher than isoniazid and rifampin and 20-fold higher than ethambutol. The rate of toxicity with pyrazinamide was 1.5 per 100 person – months compared with 0.5 per 100 person – months for isoniazid. Pyrazinamide rashes attributed to pyrazinamide may have led to in appropriate drug discontinuation. It seems that pyrazinamide-related rashes usually resolve spontaneously and not considered a reason to stop therapy. While in this study the rate of toxicity of pyrazinamide was higher than isoniazid and rifampin. Therefore, causative drugs like pyrazinamide, isoniazid and rifampin was stopped, because they induced hepatitis, which increase risk of liver damage. However, ethambutol and streptomycin were continued in this study.

In case of skin rashes, pyrazinamide was responsible drug but it was discontinued from therapy, skin rashes were improved after three weeks.

                There was a difference between this study and Menzies study may be due to short duration of study period, difference in number of patients studied. Moreover, his study conducted in United States of America. In this study there was a short duration of study and small selected number of patient and many environmental factors were involved. The patients selected in this study belong to poor socioeconomic class and they could not repeatedly visit Doctors for their checkup the occurrence of side effects of antituberculous drugs.

The British Thoracic Society (1998) guides that if the aspartate aminotransferase and alanine transferase are two or more times normal, liver function should be monitored for two weeds, then two weekly until normal. If the aspartate aminotransferase and alanine transferase under two times normal, liver function should be repeated at two weeks. If the aspartate aminotransferase and alanine transferase level rises to five times normal or bilirubin level rises, rifampin, isoniazid and pyrazinamide should be stopped. Alternative treatment will need to be considered if the patient is unwell or is smear positive and within two weeks of starting treatment.

Reactions most frequently observed with intermittent regimens of rifampin are cutaneous syndrome consisting of flushing and/or pruritus, with or without rash, involving particular face, and scalp, often with redness and watering of eye (Fried et al., 2004). Pyrazinamide produce GIT reactions, cutaneous reactions and sidero blastic anaema (Harries, 2004).

The results of this study matches with the study of Pelletier et al (2003), who observed the side effect of antituberculous drugs in 4.30 patients between 1990-99. They stated that the major adverse reaction of first line antituberculous drug, which results in discontinuation of that drug, has severely implication. They may be considerable morbidity even mortality particular may drug-induced hepatitis. Alternative agents may gave greater problems with toxicity and often less effective so that treatment must be prolonged, with attendant challenged to ensure complains as a risk of treatment failure and relapse are higher. In their results, only 37 patients had major side effects on six occasions. Severe hepatitis resulted in discontinuation of the isoniazid and pyrazinamide and neither were restarted. In three instances (two of rash and one of the severe gastrointestinal intolerance). Rifampin and pyrazinamide were stopped not rechallenged. They observed the rifampin did not commonly cause the drug-induced hepatitis. The drug mostly responsible for occurrence of hepatitis or rash during therapy of antituberculosis in tuberculosis hepatitis or rash during therapy of antituberculosis in tuberculosis patients was pyrazinamide.

                In this study, pyrazinamide manifested more side effects than other antituberculous drugs were documented according to age and gender. But incidence of drug-induced hepatitis was observed more in isoniazid than other antituberculous drugs. The rifampin had shown less side effects than other antituberculous drugs.

                The occurrence of side effects in the present study was noted to be much higher than the study done by Pelletier and colleagues. In this study there is a short duration of study and small selected number of patient and many environmental factors were involved. The patients selected in this study belong to poor socio-economical class and they could not repeatedly visit Doctors for their checkup the occurrence of side effects of antituberculous drugs.

Hepatotoxicity is one of the most serious adverse effects of anti tuberculosis drugs (ATD). Although many risk factors gave been associated with antituberculosis drugs induced hepatotoxicity, their influence on hepatitis severity has not been studied systematically. This study evaluated whether the presence of hepatotoxicity risk factors (advanced age, chronic liver diseases, abuse of alcohol or other drugs or malnutrition) influences the severity of ATD induced hepatotoxicity (Villar et al., 2004).

The results of present study match with the study of Fernanoted it al (2004). Their prospective cohort study of 471 active tuberculosis diseased patients treated with isoniazid, rifampicin and pyrazinamide were followed in tuberculosis clinic between January 1998 and July 2002. The incidence of antituberculous drug induced hepatitis was 18.2% patients in a risk group and 5.8% patients in non-risk group. Antituberculous drug-induced hepatitis is a significant and more severe in patients with risk factors. Our study correlates with this study because our big part of population live in a risk factor i.e., poverty, malnutrition, lack of clean water, combine family structure, high prevalence of viral hepatitis. So in our study there were more cases of hepatitis due to pyrazinamide, isonaizid and rifampin gave been responsible for drug-induced hepatitis.

Manifestations of hepatotoxicity include a symptomatic elevation in serum aminotransferase, jaundice and liver tenderness. One recommendation for monitoring for rifampin and pyrazinamide induced hepatitis is to determine the levels of aminotransferase at baseline and at 2, 4 and 6 weeks of treatment and to discontinue rifampin/pyrazinamide when there is (a) serum aminotransferase level that exceeds five times the upper limit of normal in an a symptomatic individual (b) any elevation of serum aminotransferase that accompanied by symptoms of hepatitis (c) any elevation in serum bilirubin (Edward et al., 2004).

The results of this study also match with the results of study carried out by Dossing et al (1996). They observed 61 patients out of 127 patients had elevated aspartate aminiotranferase after the treatment of antituberculous drug. Most of these were men with daily alcohol consumption of 60 g. Hepatitis were confirmed by challenged with pyrazinamide 7 and isoniazid 6 cases.

In the present study, we monitored that occurrence of untoward effects of antituberculous drugs. There was a difference between two studies due to short duration of study and small selected patients. In this study, the cases of hepatitis were recorded more than the study done my Dossing et al.

                This study also matched with the study of Ferner (1990). He observed that ethambutol dose related toxicity. He reported sub clinically impairment of color discrimination relatively common in 54 patients received about 15 mg/Kg/Day of ethambutol as a part of antituberculous therapy. In the present study, the ethambutol produced the opticneurites in high percentage than the Ferner’s study. But similar results were observed in old age patients group who were affected more in both studies. The peripheral neuropathy has been reported in 3 tubercular patients who had receiving the athambutol by 13 to 50 mg/Kg/day.

Peripheral neuropathy was manifested by ethambutol in our study. There were 7 reactions of peripheral neuropathy produced by ethambutol but these reactions were reversible after stoppage of ethambutol.

                In patients prescribed ethambutol it is recommended that after obtaining baseline visual acuity and color perception tests, these tests be repeated every 4 to 6 weeks, especially with new visual symptoms (Chan et, 2004).

                Zinc is found in high concentration in choroids, retina, and ganglion cells and is used by retinal dehydrogenase for transformation of retinal. This last step is important for color vision. Most case of color toxicity are bilateral and result from a dose related retro bulbar optic neuritis that can either axial or peripheral. Axial neuritis involves the papillomacular bundle. It reduces visual acuity and causes central scotomas and color vision deficits. The peripheral visual field deficits but stable visual acuity and color vision (DorothyNahm Friedberg et al.,2004).

                Ellard et al (1976) in their study observed the occurrence of joint pain on a reduction of renal elimination of urate in man caused by administration of pyrazinamide.

                The urinary excretion of pyrazinamide, pyrazinoic acid, 5-hydroxypyrazinoic acid and uric were determined in healthy subjects after giving single or multiple doses of pyrazinamide or its metabolites pyrazinoic acid. The results obtained demonstrated that 5-hydroxypyrazinoic acid is major metabolite of pyrazinoic acid in man and supported previous evidence under that retention of uric acid caused by the administration of pyrazinamide is mediated by pyrazinoic acid. After giving 3 g pyrazinamide the urinary excretion of uric acid was maximally suppressed for 24 hours. Prolonged exposure to pyrazinoic acid resulted in a net reduction in the urinary excretion of uric acid. The finding suggested that the degree of uric acid retention in patients treated with pyrazinamide containing regimens could be reduced by giving pyrazinamide intermittently (Ellard et al., 1976).

This study matched with study conducted by Ellard and coworkers. Pyrazinamide was responsible for joint pain for different age group and gender in the present study. The old age group was commonly affected by pyrazinamide.

                In a study of Hussain et al (2003), ocular reaction and toxic neuropathy were produced by ethambutol in patient’s age between 11 to 80 years. The defected color vision was fouced in 76% of eyes and 27% of eyes had defect in color vision inspite having visual acuity of 6/9 or 6/6. Dilated fundus examination revealed normal optic disc in 66 (67%) of eyes, disc pallor in 27 (28%) of eyes and 4 (4%) eyes had swollen by hyperemic disc.

                The results of present study matched with the results of study conducted by Hussain and coworkers because the ethambutol was effected in the same pathogeneses in old age group.

                Ethambutol is an effective treatment for tuberculosis. It can cause a multitude of dose and time dependent ocular side effects including color changes, visual field defects, and either unilateral or bilateral optic neuritis. Gradual decreases in central visual acuity and green red color vision problem (or less commonly blue yellow color vision defects) have been reported. These defects continue to progress for 1 to 2 months after drug is discontinued (Katherine, 2002).

                This study was also correlated with the study of Mehta (1996). He observed thrombocytopenia in three patients of pulmonary tuberculosis during therapy. Rifampicin was causative drug. The immunological studies in all three patients showed the presence of antiplatelets antibodies reaction resulting in thrombocytopenia.

Moreover, binding of these antibodies to platelet membrane was more avid in presence of rifampicin. In present study, thrombocytopenia was major side effect of rifampin in different age and gender groups. These three patients were separated on the bases of blood complete picture and clinically showed bleeding from nose, petechial rashes and bruises. The pyrazinamide was stopped and it did not reintroduced in these cases.

                Tuberculosis is a granulomatous disease, caused by mycobacterium tuberculosis. As world Health Organization estimates more than 300,000 new cases of tuberculosis develop in Pakistan every year. Cure of infectious cases of tuberculosis is the key to effective control of the disease. Treatment of tuberculosis patients reduces suffering and, if adequately, prevents death from tuberculosis. The first tine of drugs used in the treatment of tuberculosis consists of isoniazid, pyrazinamide, rifampin, streptomycin, and ethambutol. The major side effects are those giving rise to serious health hazards, and require discontinuation of the drug and referral to chest physician. Minor side effects cause relatively little discomfort; they often respond to symptomatic or simple treatment but occasionally persist for the duration of drug treatment. Chemotherapy should be stopped or temporarily interrupted only of severe drug intolerance or toxicity occurs. In fact tuberculosis drugs are relatively toxic and mild side effects are not uncommon but most do not warrant drug withdrawal.

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Ann M Ginsberg. What new in TB vaccine? Bulletin of WHO 2002; pp. 483-488.

Arther C Guyton, John D. Pulmonary ventilation In: “Hall Medical Physiology” 10th edition Philadelphia WB Saunder Company 2000; pp.432.

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Chan KL, Chan HS, Lui SF, Lai KN. Recurrent acute pancreatitis induced by isoniazid. Tubercle and Lung Disease 1994; 75:383-385.

Cheema MA. “Anti Tubercular drugs” Multi author test book of pharmacology and therapeutics” Vol. II, Lahore, National Medical Publication, 2000; pp. 368-370.

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D Marsh, B Hashim, F Hassany and L Hussain. Front line management of pulmonary tuberculosis: analysis of tuberculosis and treatment practices in urban Sindh, Pakistan. Tubercle and Lung Disease 1996; 77:86-92.

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Dick Menzies. Respiratory epidemiology unit, side effects of common anti-tuberculosis drugs. Am J resp Crit Care Med 2003.

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lalaghulamrasool bhurgri

Traveling is fun and full of excitement. It’s a passion with most people, who like to travel across the globe and see the magnificent plethora of sights and sounds abundant in this fascinating world. These days, with Lowest Tickets, traveling and vacationing in different parts of the world has been made very easy and affordable for most people.

 

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Alexander

Flying can be a major problem for people who suffer from anxiety attacks. An innovative pre-flight treatment though could be a way forward. It’s a combination of downloadable course with expert coaching.

However, the real stress and anxiety treatment takes place at a resort in Kenya. At Kas Mottani nestled around a freshwater lagoon on the Indian Ocean. The huts are open to the breezes, and contain one enormous bed, which was also very comfortable, with a huge mosquito net.

The de-stress and anxiety treatments consist of yoga and relaxation, plus individual and group sessions of CBT to help people understand more about their condition and develop their own program to eliminate

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I came across these fascinating pictures on a fashion photography blog. Not fashion photography at all, but a record of life in 1930’s Kenya taken by the great-great uncle of Oliver Prout the fashion photographer behind the UK based Fashion Photography blog.

These kinds of scenes have largely disappeared, except in the remotest areas - indeed even when I was actively traveling and studying in the region relatively recently, Western influences in dress and transport and of course education, have led to major changes in rural life.

Towns and cities have of course changed even more.