Key Words: DTP; Saudi; adverse events; vaccine;, immunization; safety; Qatif

Saudi Arabia has achieved, during the last three decades a tremendous achievement in terms of basic vaccination coverage.1 This has been carried out, mainly, by structured vaccination programs delivered, mainly, through a wide network of primary health care centers.

However, a debate is rising about the safety of this program, especially, in the absence of effective surveillance of adverse events.

This study was undertaken to survey the adverse encounters following DTP vaccination and to compare them with the internationally published figures.2-13 This comparison may serve as an indicator for safety of the practice.

In Saudi Arabia, the incidence of such reactions related to licensed vaccines has not been determined before.

A population of more than 350,00014 individuals is served by 26 PHC centers in Qatif District. All of these centers provide vaccination services for whole population in their assigned catchment areas. A total number of 18,898 doses of DTP vaccine were given to children 0 to 2 years old, in the year preceding the study.15

A weighted, systematic, random sample of 6 (23%) PHC centers were chosen after stratification by the total number of doses of DTP vaccine given in the year preceding the study, in each center.
In each sampled center, one out of four Saudi infants and children aged 0 to 2 years routinely attended for DTP vaccination, and were included using systematic random sampling, in the period from 2 Sep 2000 until 1 Sep 2001.

Informed consent was obtained from parents or companions to conduct the surveillance of adverse events following immunisation (AEFI.) A leaflet was handed to the companion for introduction of the study, as well as instructions for monitoring AEFI. Companions who refused to be included in the study were not replaced.

A study nurse filled a basic data questionnaire (no. 1) at the time of vaccination. The questionnaire contained 37 elements about demographic data, type of feeding, past and present medical history, weight, temperature, previous AEFI, education level of the mother, dose number of DTP, experience of vaccine provider, timing of vaccination, site of vaccination, needle size and manufacturer, any medication given pre or post vaccination, and any massage given to the child post vaccination. Preferable timing of phone calls was agreed upon with the companion.

The companion was asked to monitor the child for fever, change in mood and behavior, general appearance, and local reactions for 3 days post-vaccination. A study nurse telephoned, daily, each family for 3 consecutive days, interviewing the mother or the guardian for AEFI in the preceding 24 hours and completing a questionnaire (no. 2.) This questionnaire contained 24 elements about occurrence of local and systemic AEFI as defined by the WHO 10, their temporal occurrence and period. Any visit to medical services for this purpose was traced, as well as the use of local applications or antipyretics.

Non-responding telephone calls were repeated, at least twice on the same day, or in the next few days, to inquire about AEFI.

One fourth of the sample was directly observed by a study nurse, to validate the observations of the mother or the guardian. For this purpose, companions were told to visit the PHCC the day following the day of vaccination.

A pilot study of the surveillance was held in a different PHCC in the Qatif area for one month. Questionnaires and methodology were modified accordingly.

Study nurses and physicians were trained on collection of data. Study PHC centers were visited frequently, to solve any obstacle facing data collection. Study nurses had frequent meetings collectively with the authors to share the experience with each other and get guidance from the authors. Data filling was verified twice by the authors.

Data were coded, entered and analyzed by the authors using SPSS package, version 10.

Data collection was interrupted in one PHCC for 6 months due to administrative obstacles in that center.

Schedules of vaccination are predetermined as per the Saudi MOH guidelines for vaccination.

Non-Saudis were excluded, due to difficulty to contact by phone and language barrier. However they constitute a small fraction of the vaccine in Qatif.14

Vaccine used was adsorbed diphtheria, tetanus, and pertussis vaccine, Pasteur Merieux SV. It was licensed and supplied by the MOH.

A total number of 4,457 injections of DTP vaccine were given to children, age 6 weeks to 2 years, in the selected six PHC centers in the period of the study out of which, 836 (18.8%; 397 females and 439 males) had been enrolled in the study. However, post vaccination clinical reaction data were collected for 749 (89.6%) injections; 47.3% of them were female. The remaining 87 (10.4%) injection recipients did not respond to repeated phone calls or had out-of-service phone lines. They did not differ, significantly, in their basic demography as well as the DTP dose.

All recipients were given one of four primary immunizations, given usually to children below 2 years of age. The number of injections given as 1st, 2nd, 3rd and 4th dose were 183 (24.4%), 182 (24.3%), 196 (26.2) and 188 (25.1), respectively. The dominant ages of recipients in each dose were 6 to 8 weeks (96.1%), three months (93.4%), five months (94.9%) and 18 months (90.8%), respectively. Trivalent oral polio vaccine and hepatitis b vaccine were simultaneously given to all and 24.1% of recipients, respectively.

The data were collected from mothers in 93.7% of the cases. Their level of education was high school or above in 429 (57.3%), while illiterates constituted 3.9%.

There was one or more AE noted following injections in 726 (96.9%) vaccinees. Local, systemic and behavioural reactions were reported following 687 (91.7%) injections, 619 (82.6%) injections, and 316 (42.2%) injections, respectively. These were further described in Table 1.

No anaphylactic reaction, anaphylactoid reaction, hypotonic hypo-responsive episode nor DTP-associated convulsion occurred. However, hypotonicity, alone, has been reported in 8 (1.1%) cases.

Incidence of excessive crying is shown in details in Table 2.

Perceived high fever and severe swelling and redness (circumferential) each occurred following less than 5% , 1%, and 1%, respectively. No abscess was reported at injection site.

Table 3 presents the temporal occurrence of AEFI with DTP vaccine. The majority (93.4%) of AE were reported in the first 24 hours following immunization.

Eight recipients had consulted a physician within the first 24 hours. Five were for fever; one for induration and redness; one for runny nose; and one for sleepiness.

Safety of vaccination practice has been questioned, and many effects have been proposed, such as lower or higher incidence of known AEFI, or the presence of unusual AE.

DTP vaccine was chosen for this purpose for many reasons. The first is that DTP-associated reactions are well studied and published in the literature, over the last fifty years. 1-9,11,12,15,17-20 Secondly, DTP is the most frequently administered vaccine to children.

In this study, identification of findings was made primarily via the caregiver. Daily contact to the caregiver might ensure reporting of adverse events of short duration that might take place. It might be argued that the caregiver might not be educated enough to report reliable data. However, no significant differences were noted between different educational levels in reporting adverse events, as shown in Table 1. On the other hand, similar methods of reporting have been used previously by many researchers.1-4,8,21

On the other hand, quantifying adverse events objectively is difficult, resource consuming, and does not cover the whole period post immunization. Adverse events, in our study, occurred throughout all time intervals in the first forty-eight hours following immunization, and were of brief duration.

The compliance rate, in this study, was high, approaching 90% of vaccinees involved.

The vast majority (91% - 96%) of them were age-appropriately immunised. Age was constant in more than 90% of each dose. This makes differentiation of incidence of AE on age not possible.
More than 96% of DTP vaccine recipients had some effect of immunisation noted. This is comparable with incidences of 93% - 96% reported in other studies. 2,25

On the contrary, few studies and reports have shown significantly lower incidence of adverse events.1,4,5,8,12,21 These differences are attributable to different methodologies or being retrospective or, merely passive reporting. Many other variables however, might add to these differences. These include differences in vaccine preparation, batch numbers, age of the child, dose schedule, and degree and timing of observation.

Most adverse events occurred in the first twenty-four hours. The majority of them were in the first six hours. These figures are comparable with similar results shown by Long and colleagues in northern America.

Local reactions were more frequent than fever, other systemic effects, and behavioural effects, in this study, and in other studies, as well.2,3,8,11

Serious adverse events, including seizures and encephalopathy were not noted. The absence of any seizure might be attributed to an insufficient sample size to trace such events, which were estimated to be less than one in every 1500 recipients.3,11

However, few studies have described similar results to this study, in higher sample size, even.2,22 Permanent neurological damage is however much less in prevalence and not within the scope of this study. It has been reported to occur once in 32,000 to 1.24 million doses. 9,11,24

Prolonged crying, defined in this study as excessive continuous crying or screaming, occurred after 24.3% of injections, while few other studies have described non-specific definition after 30 to 63% of injections.25-27

According to our definition, crying for more than 30 minutes and crying for more than 3 hours occurred in our study, after 2.9% and 0.8% of injections, respectively. These figures are comparable with other studies that showed incidence of 2 to 6% and 0.1 to 3%, respectively.3,28

Series number of DTP dose appears to affect the incidence and type of AE. Fever, local swelling and redness, anorexia, fussiness, and hypotonia occurred maximally after DTP4, with slight decrease in their incidence after DTP2. These findings are comparable with similar findings in other studies.2,3,23,25,27

Incidence and nature of adverse events following DTP vaccination in Qatif PHCC are similar to internationally reported figures. They are common, and worth considering by health workers, in order to orient caregivers for their possible occurrence at time of vaccination.

The absence of any serious AE might necessitate a larger sample size to be traced.