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Another remarkable feature related to Tarivid launch was its use in Typhoid (Enteric fever).

In Vitro parameters favored the use of ofloxacin in enteric fever. Salmonella typhi, the causative pathogen had high sensitivity to ofloxacin. In addition, ofloxacin had high concentration in related tissues. It meant that ofloxacin should be highly effective in enteric fever.

Pakistan has had a longstanding history of typhoid fever. Several areas such as Dera Ghazi Khan and some areas in Sindh were endemic. The incidence was very high in these areas, but Typhoid fever occurred widely in the entire country, particularly during summer. There were two problems associated with enteric fever. One was the high rate of incidence and the other was increasing resistance to treatment.

Typhoid is difficult-to-treat infection anyway. The causative pathogen Salmonella typhi is not sensitive to many antibiotics. It resides in hepato-biliary system even after there is remission of acute symptoms. Several patients become carriers. Carriers are asymptomatic but can infect other healthy people and can themselves get re-infected quickly. If not treated successfully, typhoid can have serious complications including but not limited to intestinal perforation. Complications, Carrier stage development, Recurrence and infectivity are major issues related to typhoid fever.

Chloramphenicol was breakthrough antibiotic which remained highly effective for typhoid for a long time. However, resistance to chloramphenicol developed over time. Either the patients did not get relief, or they were relieved of acute symptoms but became carriers. These patients had recurrence in every season. Sulphamethoxazole/trimethoprim combination and high dose of amoxicillin were also used with variable results.

The overall scenario of typhoid occurrence and treatment was problematic at the time.

Tarivid did not have enteric fever as an approved indication. Ofloxacin was research product of Daiichi Japan. It was taken up by Hoechst and developed for marketing. It was understandable because the pre-marketing trials were conducted in those areas of the world where typhoid fever was not prevalent, hence the absence of typhoid fever from approved indications.

Hoechst initiated discussions with the physicians and gastroenterologists for using Tarivid in the treatment of typhoid fever. Many of them agreed.

The initial results were almost miraculous. Most acute patients became symptom free within seventy-two hours. Chronic patients not responding to other treatments (including treatment with chloramphenicol) were treated successfully. The market became abuzz with the new treatment option which appeared better, surer, and dependable.

With this initial success, it was imperative that the patients be documented, and more proper data be collected about treatment. The process was initiated. A huge amount of data was collected over time.

Tarivid was launched in April 1987. By the time, the treatment for typhoid was discussed and taken up, the peak season for typhoid was almost over. The number of cases declined but there were enough patients to make initial impression. By the time, the typhoid peak came in 1988, Tarivid had established itself as a treatment option to be reckoned with. Huge number of cases were treated in that year and later on, with consistently unfailing results.

Physicians reported other important results also. Patients who had history of recurrence became cured and free of recurrent disease. Patients with a history of being carriers, became free of this burden.

As mentioned earlier, quinolones were not recommended for children below twelve years of age. In some typhoid cases not responding to other treatment, Tarivid was given based on risk-benefit analysis. It did cure all such cases.

Tarivid changed the face of typhoid treatment completely. Salmonella spread through contaminated food and water which was a civic problem. It was multiplied and sustained by carriers involved in food handling; the workers in food and catering services. Tarivid could not reduce the incidence of typhoid fever but it did help to reduce morbidity, duration, multiplication, recurrence, and carrier stage development significantly.

Tarivid in typhoid was an extremely important breakthrough of the time; one with long standing implications and benefits……

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