Vaccination timeliness and delay in low- and middle-income countries: a systematic review of the literature, 2007-2017

This paper was the culmination of 2+ years of research, and a newly emerging field of vaccination literature: looking at the timeliness of vaccinations.

Worldwide, especially in low- and middle-income countries (LMICs), vaccine performance is usually assessed by measuring vaccine coverage, specifically the proportion of children who received the third dose of diphtheria-tetanus-pertussis (DTP3) vaccine, by a benchmark age (usually 5 years).

There is a major problem with measuring vaccine performance this way: Children who received their DTP3 dose on time (at 14 weeks) are counted the same as children who received their dose four years late (as long as it is received by age 5). This ignores vaccine delays, even though children who receive their vaccines late are unprotected from these diseases until they get their dose.  Ignoring timeliness thus ignores this prolonged susceptibility to infectious disease which accompanies late vaccination.

Recently, there has been a trend in the vaccination literature to start discussing timeliness, accounting for whether  these vaccinations were administered according to local schedules. However, there are a few issues with these timeliness studies:

1. Each country has their own vaccination schedule

2. There is no universal definition of “delay”, so the studies which examine timeliness use a variety of different cut points. This limits the ability to draw any comparisons across different studies, different countries, and different vaccines.

We wanted to do a systematic review, a specific type of review article which follows guidelines (PRISMA) that require higher quality of reporting and transparency. We felt this systematic review would help to identify the landscape of studies which look at vaccine timeliness to identify unmet needs in this field.

The goal of this systematic review was to search the literature, identify relevant papers, and summarize the different ways in which vaccine timeliness is measured in LMICs to make recommendations about how to measure timeliness in the future. 

We screened 1131 articles for inclusion, and ultimately selected 67 papers. As can be seen in Figure 1, below, from 2007-2017, there were noticeably more papers published concerning vaccine timeliness starting in 2014, which might be an indication that this metric is gaining traction in the vaccine world!

Though our review included papers from every World Health Organization (WHO) region, the represented papers were heavily skewed towards the African Region. These papers thus don’t represent the state of vaccine timeliness among LMICs in the European, Eastern Mediterranean, South East Asian, and American Regions. Timeliness studies are especially needed in South and Southeast Asia given the population concentration there and large burden of vaccine-preventable diseases.

There was also wide variety in the vaccine antigens (i.e. the identity of the disease that the vaccine is engineered against) that were explored, the age of children studied, and the predictors used to assess timeliness. The most frustrating was the wide variety in the definitions of timeliness itself. Papers typically assessed vaccine delay as either continuous (i.e. how many days was a dose delayed), or categorical (was it delayed or not).

These categorical definitions required creating a benchmark date at which a dose was considered delayed. This was where the extreme variability came in. Most studies used a benchmark of about 1 month. Of the 21 papers which used a fixed definition of delay (i.e. the same delay for all doses), 18 of them (86%) used 1 month. Even the month was operationalized differently by different researchers: 1 month, 4 weeks, 28 days, 4.3 weeks, or ‘within the same month’ as recommended. A lot of papers also used a benchmark of 1 day or 24 hour delay for birth doses like Hepatitis B. Other papers also used definitions of delay as 1 day past scheduled, 1 week past scheduled, and 2 weeks past schedules. Finally, a few papers didn’t use delay from the scheduled dose, but rather based on the interval which elapsed between doses.

Conclusions

Vaccination timeliness can be considered as both continuous (e.g. mean number of days delayed, or average age at which a dose was received) and categorical measures (e.g. % with timely dose).

Due to significant differences in vaccine schedules between countries and no official statement on what constitutes a “timely” dose, a continuous measure may be more appropriate to measure delay to facilitate comparison across studies.

If a categorization is desired, multiple analyses with different definitions (e.g. based on 1 week and 1 month) is preferred in the absence of any country-specific guidance on timeliness, otherwise different definitions of delay make it difficult to compare findings across studies.

 

Read the study here