In reviewing research on the safety-testing of the Ped-O-Jet, the faults of this widely-used device have emerged. These are issues extending beyond the complaints of the Ped-O-Jet being too heavy for delivering hundreds to thousands of inoculations, issues with the nozzle orifice clogging too easily and the gun’s necessary need for routine maintenance. Without question such performance issues would affect the safety of the device. However, we are focusing on the inherent faults that prevent the Ped-O-Jet from ever being called safe.
I. The Ped-O-Jet failed to deliver its full dosage during jet injection as vaccine was used for hole formation.
- Campbell and Le Roux (1969) were cognizant that the Ped-O-Jet failed to deliver its full dose and compensated for this loss when administering typhoid vaccinations amongst school-aged children. Campbell said, “the advantage of large over small doses…[was] to compensate for the slight loss of vaccine which occurs with the Ped-O-Jet method” (Campbell & Le Roux, 1969).
- A researcher for the World Health Organization noted a significant loss of vaccine when using Ped-O-Jets in his 1971 report on Yellow Fever vaccinations. Dr. Y. Robin noted, “The quantity of liquid expelled can be regulated from 0.1 to 1 ml. Owing to the reflux caused by the elasticity of the skin, in order to inject 0.10 ml it is necessary to eject 0.15 ml (Dull, 1968)” (WHO, 1971). Therefore, during the late 1960s, researchers noted that 33% (0.05 ml) of the vaccine was refluxed, or rather flowed back out of the skin. This reflux of vaccine, tissue juices and blood was a major breach of sterility since the jet injector was either pressed firmly against the skin or was in close proximity.
II. Wiping the external surface of the Ped-O-Jet’s nozzle did not prevent cross-contamination. Whether the nozzle was wiped or not wiped transmission of relevant volumes of blood capable of transmitting blood-borne pathogens were observed (Grabowsky et al., 1994; Hoffman et al., unpublished). This was due to a phenomenon called retrograde flow.
III. Retrograde Flow. During the end of jet injection process, the pressure of the jet stream impinging the skin would be less than the pressure of the fluid deposited within the newly constructed hole in the vaccinee’s arm. Since the jet stream was too weak to further deepen the hole, the deposited fluid moved backwards and flowed out of the hole and back into the jet injector. This would be an undesirable, yet expected phenomenon in almost every jet injection due to the continuous depletion of pressure.
- Joy Baxter and Samir Mitragotri both described the mechanical workings of jet injection in their 2006 paper. Baxter, a researcher for Unilever Research and Development, and Mitragotri, a chemical engineer at Harvard University, wrote, “Backflow of the jet is observed during hole formation if the volumetric rate of hole formation in the skin is smaller than the volumetric flow rate of the jet liquid into the skin” (Baxter & Mitragotri, 2006).
- In 1997 the World Health Organization (WHO) hypothesized of retrograde flow as preliminary data from safety tests were reported. The WHO stated,
contamination of the fluid path occurs along the jet-stream at the end of the shot when pressures in the liquid column at the site of the injection begin to exceed the pressures at the injector head…Similar conclusions can be reached from the results of parallel tests in-vitro on the PED-O-JET (now AM-O-JET) at the Programme for Appropriate Technology in Health (PATH – USA). These tests confirmed a correlation between the extent of contamination and the level of back-pressure in simulated skin models (WHO, 1997).
- Peter Hoffman studied cross-contamination via jet injectors at the request of the WHO and found retrograde flow within his laboratory investigations of the Ped-O-Jet. Hoffman stated,
some of the liquid injected form[ed] a pocket below the injection site. This will be under maximum pressure towards the end of the injection process, before sufficient dispersion into surrounding tissues has occurred to release pressure. This will coincide with a lessening of pressure from the injector. When the pressure from the injector is exceeded by the back-pressure from the tissue pocket, backflow through the pathway in the skin created by the injector could occur. This liquid will contain blood from the destruction of small blood vessels during the injection process and can have different pathways after it has emerged from the skin according to the type of injector. Injectors that have direct skin contact will form a continuous fluid pathway between the skin and injector. As the outward pressure from the injector dies away at the end of an injection, back-pressure from the fluid in the tissue pocket will cause blackflow out of the skin to inside the injector’s fluid pathway (Hoffman et al., 2001).
- In quoting Rebecca Voelker who paraphrased it so simply, “Hoffman said jet injection builds pressure in the skin that is greater than the pressure in the injector, causing a small backflow of blood onto the device” (Voelker, 1999).
- In 1977, researchers Philip Neufeld and Leon Katz from the Bureau of Medical Devices at Canada’s Department of National Health and Welfare studied the Ped-O-Jet. The researchers noted “a low-pressure ‘tail’ at the end of the injection” (Neufeld & Katz, 1977). Here is evidence that low-pressure at the end of the injection existed in the Ped-O-Jet in the 1970s during the height of this device. The low-pressure at the end of the injection indicates the likelihood of retrograde flow, in which the vaccine, commingled with blood, went back into the Ped-O-Jet.
- Dr. Robin wrote about “reflux” when using Ped-O-Jets in his 1971 WHO report on Yellow Fever vaccinations. Dr. Robin noted,
The quantity of liquid expelled can be regulated from 0.1 to 1 ml. Owing to the reflux caused by the elasticity of the skin, in order to inject 0.10 ml it is necessary to eject 0.15 ml (Dull, 1968). This ejected volume was measured by weighing on a precision balance. The volume did not vary, throughout the operations, by more than +/- 5.3%, which is no greater than in the case of injection by syringe (WHO, 1971).
Here, Robin and Dull were noting the loss of vaccine during hole formation which occurred at the beginning of the jet injection. The use of the word “reflux,” meaning the backwards flow of a liquid, demonstrates that Robin and Dull both knew the vaccine flowed backwards. Granted these researchers did not know of the full effect of retrograde flow; however, Robin and Dull did state due to the elasticity of the skin the fluid was not absorbed within the body but moved backwards and out of the body.
IV. The Ped-O-Jet’s check-valve did not prevent fluid and blood on the nozzle tip from being sucked back into the internal fluid pathway and drug reservoir.
- Inventor of the Ped-O-Jet, Aaron Ismach, stated within his 1959 patent that his invention is “free from danger of sucking fluid back from a patient either during or after the firing cycle is completed so that the danger of cross-infection is almost completely avoided” (Ismach, 1962). His assertion reveals MUNJIs faced issues with check-valves. Subsequent research has revealed the Ped-O-Jet was no exception to this inherent design fault.
- In 1977, CDC’s Hepatitis Laboratories Division conducted safety testing on the Ped-O-Jet. The researchers observed a drop of fluid remained on the injector nozzle after firing and would disappear back into the nozzle orifice within 3 to 5 seconds. The researchers concluded, “These manipulations causing disappearance of the fluid drop are common during clinical use of the jet injector” (CDC, 1977).
- In 1994, the CDC retested the safety of the Ped-O-Jet. After artificially contaminating the underbelly of a shaved rabbit with Hepatitis B surface antigen (HBsAg), a sterile Ped-O-Jet was placed upon the site and administered an injection. The subsequent injection was fired into a vial and tested for HBsAg. The results found the ejected fluid of the next shot fired was positive for HBsAg in 19 out of 50 (38%) of the samples (Grabowsky et al., 1994). Cross-contamination of HBsAg from the skin surface to the ejectate of the subsequent shot was due to either fluid suck-back or retrograde flow.
- The CDC collaborated with American Jet Injector Corporation and the University of Florida to test the safety of the Am-O-Jet, a MUNJI device. The Am-O-Jet was an identical design of the Ped-O-Jet. Within this study the researchers admit the check-valve had been redesigned; thus further implicating the inherent design faults of previous Ped-O-Jet models. It is noteworthy to add, the researchers found rates of contamination were significant with the Am-O-Jet (Sweat et al., 2000).
V. Every time the Ped-O-Jet became contaminated it remained contaminated for the following two consecutive shots. This means once the Ped-O-Jet became contaminated with blood, the next two people in line would be exposed to that blood. Once the Ped-O-Jet became contaminated with a blood-borne pathogen, the next two people in line would be exposed to that blood-borne pathogen.
- CDC’s 1977 investigation of the Ped-O-Jet found, after the nozzle was contaminated, the ejected fluid of the next shot fired was positive for HBsAg in 4 out of 5 (80%) of the samples. The second shot fired after the nozzle was contaminated was positive in 3 out of 5 (60%) of the samples. The third, fourth and fifth shots fired were all negative. These results indicated that once the Ped-O-Jet became contaminated it remained contaminated for the next two consecutive shots (CDC, 1977).
- CDC’s 1994 investigation of the Ped-O-Jet administered a sterile injection to the underbelly of a HBsAg-contaminated rabbit and then administered a subsequent shot into five vials. The test was repeated 10 times. So each test consisted of five samples and ten tests were conducted creating a total of 50 samples. The researchers only reported that 19 of the 50 samples were HBsAg-positive indicating that more than just the first shots were contaminated. We can presume that all ten of the first shots were positive and therefore nine of the seconds shots tested were positive (Grabowsky et al., 1994).
- In WHO’s 1998 field trial in Brazil, researchers administered a Ped-O-Jet injection to patients infected with Hepatitis B and Hepatitis C. After administering an injection, the subsequent three injections were fired into three separate vials. Results found that 13 out of 117 (11.1%) of the subsequent first shots contained more than 10 picoliters of blood. Results of the second “shot” found 4 out of 117 (3.4%) of the samples were positive and the third “shot” found no contamination (Hoffman et al., unpublished).
VI. In studies upon humans, cross-contamination of blood occurred via the Ped-O-Jet despite the lack of visible bleeding at the injection site or any visible blood contamination upon the Ped-O-Jet’s nozzle.
- The Brazilian Ministry of Health conducted a study to assure the safety of the Ped-O-Jet during routine military vaccinations in 1991. The researchers found, “there was little to no correlation between visible bleeding and detection of occult blood in the successive vaccine doses. Only one person had both” (de Souza Brito et al., 1994; de Souza Brito, 1996). There was no visible bleeding at the injection site in 27 out of 28 (96.4%) of the ejectates which contained blood, indicating blood transferred within microscopic levels not visible to the human eye.
- In 1998 the WHO chose to replicate the Brazilian study. In this field trial, human volunteers infected with Hepatitis B and Hepatitis C received an injection with a Ped-O-Jet injector. There was no visible bleeding at the injection site in 14 of the 29 (48.2%) of the ejectates which contained blood. Of which 11 samples of no visible bleeding were the first shot after becoming contaminated and 3 samples were the second shot after becoming contaminated (Hoffman et al., unpublished).
This same phenomenon has been observed within other jet injector models. Even though these other studies did not use the Ped-O-Jet, they demonstrate the occurrence of cross-contamination despite the lack of visible bleeding is an established and systemic phenomenon associated with jet injection.
- In a Dutch study, researchers assessed the degree of cross-contamination after using a Med-E-Jet injector on mice chronically infected with lactic dehydrogenase virus (LDV) [better known today as lactate dehydrogenase virus], a highly infectious pathogen. Results found 16 out of 49 (33%) mice became infected with the LDV virus after receiving injections from a Med-E-Jet injector. Most shockingly, researchers observed “post-injection bleeding was relatively uncommon,” occurring in only two out of 49 (4%) of the mice. Assuming the two bleeders were amongst the mice who became infected with LDV, indicates at least 14 out of 16 (88%) of the mice became infected despite the lack of visible bleeding (Brink et al., 1985).
- A field trial for a protector cap needle-free injector, known as the HSI-500 and as the JIMI, upon humans infected with Hepatitis B found the Hepatitis B virus was cross-contaminated regardless of the single-use protector cap being placed over the nozzle. The study also found, there was no visible bleeding at the injection site in 7 out of the 17 (41.1%) injections that tested positive for Hepatitis B. This indicates that cross-contamination of Hepatitis B virus successfully occurred within microscopic levels of blood not visible to the human eye. This study also demonstrated that Hepatitis B was able to permeate the single-use protector cap and enter the jet injectors internal fluid pathway (Kelly et al., 2008).
These inherent faults, as described above, are evidence the Ped-O-Jet allowed cross-contamination of blood and blood-borne pathogens between subsequent vaccinees. The Ped-O-Jet was not superior to any revival device but suffered the same undesirable effects that impacted all jet injectors.
- (Baxter & Mitragotri, 2006) Baxter J, Mitragotri S. Needle-free liquid jet injections: mechanisms and applications. Expert Rev Med Devices Sep 2006;3(5):565-74.
- (Brink et al., 1985) Brink PRG, van Loon AM, Trommelen JCM, Gribnau FWJ, Smale-Novakova IRO. Virus transmission by subcutaneous jet injection. J Med Microbiol. December 1985; 20(3): 393-397.
- (Campbell & Le Roux, 1969) Campbell JM and NJ Le Roux. Control of Typhoid Fever By Vaccination. S.A. Medical Journal, 15 November 1969; pp. 1408-1411.
- (CDC, 1977) CDC. DHEW Memorandum: Informal Quarterly Report of October-December 1977. From: Special Investigations Section (Petersen NJ, Bond WW, Carson LA) to: Deputy Director (Favero MS), Hepatitis Laboratories Division, Phoenix, AZ (unpublished).
- (de Souza Brito, 1996) de Souza Brito G. Multi dose jet injectors and safety aspects in Brazil. CDC & WHO Meeting on Jet Injectors. Atlanta, October 2-3, 1996. (communication paper).
- (de Souza Brito et al., 1994) de Souza Brito G, Chen RT, Stefano IC, Campos AM, Oselka G. The risk of transmission of HIV and other blood-born diseases via jet injectors during immunization mass campaigns in Brazil. 10th International Conference on AIDS, Yokohama, 7-12 August 1994;10(1):301 (abstract no. PC0132, http://www.aegis.com/conferences/10wac/pc0132.html).
- (Grabowsky et al., 1994) Grabowsky M, Hadler SC, Chen RT, Bond WW, de Souza Brito G. Risk of transmission of hepatitis B virus or human immunodeficiency virus from jet injectors and from needles and syringes. Unpublished manuscript draft, dated January 3, 1994.
- (Hoffman et al., unpublished) Hoffman PN, Abuknesha RA, Andrews NJ, Brito GS, Carrasco P, Weckx LY, Moia LJMP, Silva AEB, Lloyd J. A field trial of jet injector safety in Brazil. (unpublished).
- (Hoffman et al., 2001) Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. A model to assess the infection potential of jet injectors used in mass immunisation. Vaccine. 16 July 2001;19(28-29):4020-4027.
- (Ismach, 1962) Ismach, Aaron. “Multi-dose jet injection device.” United States Patent 3,057,349. 9 October 1962.
- (Kelly et al., 2008) Kelly K, Loskutov A, Zehrung D, Puaa K, LaBarre P, Muller N, Guiqiang W, Ding H, Hu D, Blackwelder WC. Preventing contamination between injections with multi-use nozzle needle-free injectors: a safety trial. Vaccine (2008) 26, 1344-1352.
- (Neufeld & Katz, 1977) Neufeld PD & Katz L. Comparative evaluation of three jet injectors for mass immunization. Canadian journal of public health, 1977, 68: 513-516.
- (Sweat et al., 2000) Sweat JM, Abdy M, Weniger BG, Harrington R, Coyle B, Abuknesha RA, Gibbs EP. Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids. Ann NY Acad Sci 2000;916(31):681-682.
- (Voelker, 1999) Voelker R. Eradication Efforts Need Needle-Free Delivery. JAMA May 26, 1999;281(20):1879-1881.
- (WHO, 1971) Robin, Y. Yellow Fever Vaccination, Alone or In Association, Using 17 D Vaccine Administered Intradermally. Geneva: World Health Organization, Expert Committee on Yellow Fever, document 2 March 1971; 1-5.
- (WHO, 1997) World Health Organization. Steering group on the development of jet injection, Geneva, 18-19 March 1997. Geneva: World Health Organization, Global Programme on Vaccines and Immunizations, document, 1997;1-37.