|Year : 1964 | Volume
| Issue : 2 | Page : 59-64
Results of antitrachoma vaccination trials in East Africa
GB Bietti1, P Guerra2, A Felici3, R Vozza1
1 Eye Clinic, University of Rome, Italy
2 Haile Sellassie 1st Ophthalmic Centre, Ethiopia
3 Institute Superiore di Sanita, Dept of Microbiology, Rome, Italy
|Date of Web Publication||14-Feb-2008|
G B Bietti
Eye Clinic, University of Rome
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bietti G B, Guerra P, Felici A, Vozza R. Results of antitrachoma vaccination trials in East Africa. Indian J Ophthalmol 1964;12:59-64
The experiments on the prevention and therapy of the trachomatous infection were started by our group in Ethiopia in 1960.
Preliminary results of these trials were already reported (1961), (1962), (1963) but only now, after 4 years, it is possible to attempt a better evaluation of the collected data.
| Materials and Methods|| |
All the vaccines used in these experiments were inactivated with 0,02% formaline and prepared from the strain trachoma Asmara 3 / 1960.
Contents of the Vaccines and Schedule of Vaccination
(a) Aqueous vaccine : Suspension of purified elementary bodies in saline to make up a final 100% YSP (Yolk Sac Pool).
Administration : First intramuscular injection 1 ml.; booster after 30 days with 1 ml. of 50%, YSP.
(b) Vaccine adsorbed on Aluminium hydroxide: Suspension of equal parts of purified and concentrated elementary bodies in saline and of aluminium (18 mg/ml) to make up a final concentration of 200% YSP. Before administration, suspension was shaken and kept over-night at + 4°C.
Administration : First intramuscular injection 0.5 ml; booster after 40 days with 1 ml of aqueous vaccine 50% YSP.
(c) Water-in-oil emulsion vaccine: Suspension of equal parts of purified and concentrated elementary bodies in saline and oil adjuvants (Arlacel A, I part, Bayol F, 9 parts) to make up a final concentration of 200% YSP. Suspension was stirred in a Waring blendor until a stable milky emulsion was obtained.
Administration: First intramuscular injection 0.5ml; booster after 40 days with 1 ml of aqueous vaccine 50 YSP. A second booster was also tested after 6 months using 0.5 ml of water-in-oil emulsion vaccine. Each of the vaccine in every experiment was prepared from a single YSP of the strain Asmara/ 3 / 1960, so that the concentrations of elementary bodies of similar amounts of viral suspensions were considered equivalent.
| Safety Tests|| |
Fifteen guinea pigs, for each type of vaccine were inoculated by the intraperitoneal route with 1 ml without evidence of harmful side effects. Deep intramuscular injection of 0.5 ml of water-in-oil and aluminium vaccine did not produce local and general alterations in five monkeys. Similar doses were found without side effects in men. A fourfold concentrated dose of waterin oil vaccine administered to one of us (A.F.) did not produce local or general alterations.
| Evaluations of the Results and Clinical Checks|| |
For a careful evaluation of the results, both vaccinated and control individuals were grouped following McCallan's classification. Within Trachoma II and III groups, light cases (f+) were evaluated separately from the more severe ones (f++, f+++).
Individuals considered as healthy were generally under 1 year of age and seldom exceeding 2 years. Only in this group we believe to exist consistent possibilities that the individuals had not been affected by the disease in an highly endemic area. Clinical checks were performed every 2 months for 1960 experiments. In the following, the first check was carried out after 6 months and then successively every year. The clinical evaluation was carried out with the following criteria :
a) Analytic evaluation
Clinical cure: disappearance of follicles
Improvement: shift from the category "severe trachoma" (f++, f+++) to "mild trachoma" (f+)
Worsening: opposite of improvement
No change: permanence in the initial category
Relapse or reinfection : appearance of follicles in an individual affected by non active (non follicular) trachoma
Infection: appearance of follicles in healthy individuals.
b) Synthetic evaluation
This evaluation considers a positive and a negative clinical course. Positive means cure or improvement in active cases, no change in trachoma dubium (D) healthy or Tr IV case) whereas a negative course means no change or worsening in active cases, relapses and/or reinfections in non active cases, infection of healthy cases, clear disease i n Tr D.
| Selection of Cases|| |
Vaccinated and control individuals were selected, when possible, in the same environment (schools, orphanages, villages and other communities) comparing cases of the same age affected by disease of comparable severity.
By this way the following groups were treated: [Table - 3]
| Environment of Vaccination Trials|| |
Year 1960-Vaccination trials were carried out in three villages at about 30 Km. from Asmara and in Keren's orphanage, about 90 Km. from it.
Both active and non active case were vaccinated. The age of vaccinated individuals ranged between two and fifteen years.
Year 1961-Vaccination trials and controls were performed in primary schools in Asmara and in the neighbouring villages. Active and non active cases were vaccinated. The age ranged between two and fifteen years.
Year 1962-Vaccination trials and controls were performed on children of the Police Constables of Asmara and neighbouring stations.
Only individuals affected by active, non-cicatricial trachoma and healthy individuals under two years of age were vaccinated. The age was generally near to or less than four years.
| Results|| |
Results were read by an ophthalmologist, ignorant of the treatment carried out. Within the limits of practical possibilities the same ophthalmologist performed the first and the following readings of every experiment.
The antitrachoma vaccines used proved to be free of harmful side-effects. Only in newborns within the first year of age, the injection of water-in-oil-emulsion vaccine gave place to a small nodule which was palpable at the time of the booster.
The results collected in the clinical checks are summarized in [Table - 1],[Table - 2]
[Table - 1] reports the results in relation to the type of vaccination while [Table - 2] is prepared with the information collected in 6 following clinical checks performed during 36 months on the subjects vaccinated with water-in-oil emulsion vaccine, which is the more widely used so far, in our trials.
As evident from the two tables, the number of vaccinated cases underwent considerable reduction during the checks, owing to the lack of cooperation and to the very marked nomadism of the Erythrean populations in the vaccinated districts. This factor accounts for the reduced size of certain figures which are reported although deprived of statistical significance.
The data reported in [Table - 1] demonstrate that vaccination without booster is scarcely effective in prevention and therapy both using aqueous and oil vaccination, although a better response was obtained with the latter. The best results were recorded with oil vaccination followed by one or two boosters, after 45 days and 6 months respectively.
Although the figures were considerably cut down by the aforementioned factors, the vaccination with A1(OH) 3 adsorbed vaccines seems to give slightly inferior results. This type of vaccination was however considered with particular attention owing to the ban of some pharmacopeias towards oil adjuvants.
The following conclusions can be drawn from an analysis of the data collected in [Table - 2]
1) The efficacy of the vaccination with oil adjuvants is conditioned by a booster shot. Simple vaccination has only a limited preventive and therapeutic activity. A second booster performed after six months with water-in-oil vaccine greatly improved the results as it is shown in [Table - 1].
2) Vaccination reduces the rate of morbidity of apparently healthy subjects for at least one year.
3) Vaccination reduces considerably for 2 years the number of cases of "trachoma dubium" (TrD) which develop a clear cut disease.
4) The relapses and/or reinfections of cicatricial cases (TrIV) are prevented considerably for about 2 years.
This point is worthy of attention in view of the possibility of using vaccination after the cure obtained by means of common therapeutic agents.
5) Active trachoma both in its It and III stage regardless of its severity, is favourably influenced by vaccination which gives place to a good incidence of favourable courses. The persistence of some cases with a very scanty number of follicles (f+) shows that the disease was controlled to a degree of severity, scarcely dangerous to impair vision.
The favourable effects of the vaccination are still detectable after 36 months, although the reduction of the size of the experiment does not allow definite conclusions on this point.
| Discussion|| |
Our experience with inactivated, monotypic trachoma vaccines in East Africa has to be considered favourable even if its efficacy is far from being absolute in its preventive and therapeutic aspects.
Many important problems are still unsolved despite the considerable information already collected in this field.
Substantial improvements could be achieved by the use of polyvalent types of vaccines, provided that the existence of strain antigenic differences will be ascertained. At the present time no undisputable information is available on this point.
Other improvements could result from the use of more concentrated suspensions of elementary bodies in different media. A trial on 10.000 cases is in advanced stage of development in Ethiopia using an AL(OH) 3 , adsorbed monotypic vaccine, concentrated fourfold in relation to the present ones.
Particular attention should also be given to the use of vaccines in association with minimal chemotherapeutic treatment. Preliminary trials the results are reported elsewhere (1963) gave particularly encouraging data.
Concluding, the experience collected so far allows us to foresee that antitrachoma vaccines will probably find their place in the near future among the valuable agents for the mass control of the disease.
Even if the results of the vaccination will turn out to be slightly inferior to those of chemoantibiotic treatment, the advantages of an easier administration and of the more lasting protection has to be taken into consideration. This is particularly true in underdeveloped countries where other prolonged general and local treatments are sometimes difficult or impossible.
| Acknowledgement|| |
This research was carried out with funds from the imperial Ethiopian Government, to which the authors are greatly indebted.
| References|| |
FELICI, A.; VOZZA, R. (1961) R. C. 1st. Sup. Sanita, Roma: 23, 1242.
BIETTI, G. B.; GUERRA, P.; FELICI, A.: VOZZA, R. (1963) Arch. Soc. Ophthal. Jan.: 66, 362.
BIETTI, G. B.; GUERRA, P.; FELICJ, A.; VOZZA, R. (1963) Orient. Arch. Ophthal.: 72, 92.
[Table - 1], [Table - 2], [Table - 3]