Introduction
Before the introduction of vaccines, diphtheria was the leading cause of death among children aged 0 to 4 years of age in the United States. Upon the introduction of vaccines after the Second World War, incidence of diphtheria reduced drastically. However, cases of diphtheria are still recorded worldwide, especially in underdeveloped and developing countries where people live in condensed and unhygienic conditions.
Diphtheria is a serious disease caused by the gram-positive bacterium Corynebacterium diphtheria which can be transmitted through airborne droplets produced when an infected person coughs or sneezes. If such droplets touch household items, sharing of such items can also cause one to get infected. In the early nineties, it was observed that diphtheria was spread among school children in Australia through sharing of pencils and pens. When one comes in contact with the bacterium, it produces a toxin which goes on to cause damage to the tissues in the area of infection. This leads to the production of a grey thick membrane. This thick membrane is often observed around the throat and tonsils leading to a difficulty in breathing. Infected individuals tend to experience sore throat, hoarseness, nasal discharge, fever and weakness. Due to the damage done to respiratory organs, the lymph nodes tend to get enlarged leading to a swollen neck. When not treated early, diphtheria toxins can spread through the bloodstream and damage other tissues such as the heart muscle. This can lead to a heart attack and eventually cause death. It can also cause nerve damage in the throat, limbs and respiratory canal. Damage to these nerves will cause difficulty in swallowing and muscle weakness. With adequate treatment, infected individuals tend to get healed however, recovery rate is lower in children younger than 5. Rates of death caused by diphtheria infection are higher in children than adults.
The year 2019 was quite a year for Africa as it recorded the highest number of diphtheria cases so far (11,400 cases). The most notable diphtheria outbreak in Nigeria occurred between February and November 2011 in Kimba, Borno state. A total of 98 cases were observed and 63 of them were children below 10 years of age. At the time of the outbreak, 98% of the infected individuals had never been immunized against diphtheria. According to the World Health Organization (WHO), only 47% of Nigerians had received up to three doses of DTP vaccine in 2011. In addition, there was a lack of diphtheria antitoxin (DAT) on national level hence it had to be imported from France. Importation problems and shipping delays contributed to the elevation of the case-fatality ratio to 21.4%. In November 2011, a vaccination campaign was held in Kimba. In January 2023, the Nigeria Centre for Disease Control (NCDC) received reports of new cases of diphtheria in Lagos and Kano. By May 2023, a total of 1439 cases had been reported and 557 cases confirmed. A total of 73 deaths were confirmed and case fatality ratio was 13%. At this time, the disease had successfully spread to 21 out of the 36 states in Nigeria as well as the Federal Capital Territory. A common symptom observed in all cases is the swollen neck. NCDC also observed that majority of the residents in affected areas were not vaccinated against diphtheria and only 12.5% of the confirmed cases were vaccinated. Osun and Lagos were observed to have high cases of zero-dose children who are at high risk of diphtheria. Due to the outbreak, there was an increase in importation of diphtheria vaccines into Nigeria. It was recorded that diphtheria cases observed in Nigeria during the 2023 outbreak reduced by up to 10% when more people got vaccinated.
Diphtheria, although a fatal disease, can be prevented by vaccination. WHO recommends that diphtheria vaccines should be taken at three stages of life; between 0 and 6 years, between 11 and 13 and the last doses at adulthood. This ensures that an individual enjoys good protection against diphtheria.
Diphtheria vaccines are toxoid vaccines. This means that the vaccine contains a toxoid gotten from the causative agent. It is often presented in combination with tetanus toxoid and acellular pertussis toxoid, and recently toxoids related to other diseases. These combination vaccines often come in various forms however, there are four major types or forms of diphtheria vaccines. They include:
- DTaP
- DT
- Tdap
- Td
- DTaP
This vaccine derives its name from the toxoids contained in it. D indicates the presence of diphtheria toxoid; T indicates the presence of tetanus toxoid while aP indicates the presence of acellular pertussis toxoid in its inactivated form. Full strength doses of each toxoid are contained in the DTaP vaccine. It is administered to children between 2 months and 6 years of age for the prevention of diphtheria, tetanus and whooping cough.
Toxins produced by Corynebacterium diphtheriae are extracted and then inactivated using formalin or any other reagent depending on the manufacturer. Inactivation of the toxins lead to the production of toxoids which when injected into the bloodstream stimulates the production of antibodies. The presence of antibodies helps the body to maintain strong immunity against each of the diseases. Just like other vaccines made with inactivated toxoids, the effect of DTaP vaccine (immunity developed by production of more antibodies) is often short- lived unlike in live vaccines. This is one of the reasons why up to five doses are administered to children at the early ages. The first dose of DTaP vaccine is administered to an infant at 2 months old. The next dose is administered at 4 months, 6 months then 15 to 18 months. The final dose of DTaP vaccine is administered between 4 to 6 years of age. At this stage, immunity to diphtheria, tetanus, and whooping cough (pertussis) is developed.
Although it varies among brands, most 0.5ml vials of DTaP vaccines often contain up to 15 to 25 Lf of diphtheria toxoid, 5 to 10 Lf of tetanus toxoid, and acellular pertussis antigen which is often 10 to 20 mcg of detoxified pertussis toxin.
- DT
The DT vaccine is similar to the DTaP vaccine. It is administered to children between 0 and 6 years in five divided doses and it is not used in individuals older than 7 years of age. The major difference between DTaP and DT is that DT does not provide enhanced immunity to pertussis. This indicates that children given this vaccine have the risk of being infected with pertussis and eventually being down with whooping cough.
DT vaccine is often administered to children who after the first dose of DTaP, develop encephalopathy which is characterized by prolonged seizures and decreased levels of unconsciousness that is not related to any underlying disease. The encephalopathy often occurs due to the presence of the acellular pertussis toxoid.
In situations where the encephalopathy is being controlled or treated, DTaP can still be administered to the child. DT is also administered in five divided doses in the same duration as DTaP. Like DT, it stimulates the body to produce antibodies which will eventually enhance immunity to diphtheria and tetanus.
- Tdap and Td
These sets of vaccines are administered to children above 7 years of age as well as adults. These vaccines contain full doses of the inactivated tetanus toxoid as in DTaP and DT. However, the dose of diphtheria toxoid and acellular pertussis toxoid present in these vaccines is half of the concentration present in DTaP.
Tdap vaccines contain inactivated acellular pertussis toxoid while Td contains only inactivated tetanus toxoid and diphtheria toxoid. The first dose of these vaccines is administered at adolescence between ages 11 and 13. The aim of this shot is to boost the immunity already developed by the DTaP or DT vaccine in the early years. Subsequent shots of these vaccines also achieve this same aim. Hence, Tdap and Td are often called booster vaccines. It is advised that shots of these booster vaccines should be taken every ten years in order to maintain immunity however, it is believed that the immunity might run out before ten years is over.
Tdap and Td vaccines can be administered to adults who have not received any dose of DTaP or DT vaccine in their early years. They will help to boost immunity to tetanus, diphtheria and in the case of Tdap, acellular pertussis. Just like in DT, Td is given to adults and adolescents who have allergies to acellular pertussis toxoid.
According to the recommendation of the Center for Disease Control, every pregnant woman should receive the Tdap vaccine between the 27th and 36th week of pregnancy. This will help to protect the woman from tetanus infection which may arise during delivery. The antibodies developed in response to the vaccine can also be passed to the fetus thereby protecting the newborn against the associated diseases until he or she can receive the DTaP vaccine at 2 months old.
In recent times, new forms of diphtheria vaccines have been developed. These new forms contain toxoids of 4 to 6 diseases. The most common new combination vaccines include Tdap-IPV (Adacel®) and DTaP-IPV (Tetraxim®) vaccines. These vaccines contain the inactivated poliovirus in addition to diphtheria, tetanus, and pertussis toxoids present. These combination vaccines protect against four out of the six killer diseases identified by the Expanded Programmme on Immunization (EPI). Combination vaccines that protect against up to 6 diseases have also been designed. The most common one (Hexaxim®) contains diphtheria toxoid, tetanus toxoid, acellular pertussis toxoid, hemophilia influenza B, inactivated poliovirus, and hepatitis B virus thereby protecting against these diseases. The Vaccine, Biologics, and Medical Devices Laboratory Directorate of the National Agency for Food and Drug Administration and Control (NAFDAC) have conducted quality control analyses on these vaccines and confirmed them fit for use in Nigeria. The introduction of these vaccines into the country helps to improve adherence to vaccination schedules which was observed to be a major problem associated with proper immunization of children in Nigeria.
The Expanded Programme on Immunization (EPI) states that every child should receive three doses of DTaP vaccine between 6 weeks and 14 weeks of age. This is lower than the recommendation made by WHO. This may be a reason for frequent diphtheria outbreaks in Nigeria. In 2014, it was observed that only 5.1% of one-year-olds had received the three doses of DTaP as recommended by EPI. 67% of parents complained of a lack of vaccines in health centers while 13% complained of the long wait between vaccines. To prevent further outbreaks of diphtheria in Nigeria, the Expanded Programme on Immunization (EPI) should be reviewed and the number of doses of diphtheria vaccine administered to children should be in line with WHO recommendation. Also, adults should be enlightened on the complications associated with diphtheria disease and the need to take booster shots throughout their life. Parents should also be enlightened on the need for vaccination, the reason for the break between vaccine shots, and the complications associated with various diseases. Measures should be put in place to ensure that the supply of vaccines to Nigeria and other affected areas is steady and reliable. Hygienic practices should be taught to residents of Nigeria especially residents of rural areas.
Conclusion
Diphtheria vaccines are a critical tool in preventing the spread of this potentially deadly bacterial infection. They have proven to be highly effective in reducing the incidence of diphtheria and its associated complications. Staying up-to-date with recommended vaccination schedules is essential for individual health and public health efforts to control the disease.
REFERENCES
- WHO, 2023. Diphtheria in Nigeria. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON452
- Ophori et Al, 2014. Current Trends of Immunization in Nigeria: Prospects and Challenges. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139536/
- WHO-OCHA, 2023. Nigeria- Diphtheria Outbreak. Available at: https://reliefweb.int/report/nigeria/nigeria-diphtheria-outbreak-dref-application-mdrng037
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- CDC, 2022. Diphtheria: Causes and How it Spreads. Available at: https://www.cdc.gov/diphtheria/about/causes-transmission.html
- CDC, 2023. Diphtheria, Tetanus, and Pertussis Vaccine Recommendations. Available at: https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/recommendations.html#:~:text=Any%20Diphtheria%20Toxoid%2D%2C%20Tetanus%20Toxoid,allergy%20to%20any%20vaccine%20component
- CDC, 2022. About Diphtheria, Tetanus and Pertussis Vaccines. Available at: https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vaccine.html#:~:text=Each%200.5%2DmL%20dose%20of%20DAPTACEL%C2%AE%20(Sanofi%20Pasteur),2%20and%203%20(FIM)%5D.
Adekunle-Segun.O., Omosimua Shedrack.O., Ajayi Toluwani
