Research Documented Presence of Blood & Risk of Hepatitis
Older scientific studies documented the presence of blood following Ped-O-Jet injections and expressed concern for possible transmission of infectious pathogens, such as hepatitis. However, the ability to detect viral hepatitis during these eras was primitive, causing the data within these studies to falsely conclude there was no cross-contamination.
- In 1959 at an international symposium on immunology in Yugoslavia, Dr. Abram Benenson reported of a mass immunization field trial with the newly invented Ped-O-Jet. In the field trial, 1,440 U.S. military personnel were inoculated with a 1 milliliter dose of influenza vaccine in a one hour period. Benenson also reported bleeding at the injection site was observed within 5 to 10 percent of injections.
Benenson and his colleagues at Walter Reed Army Institute of Research had expressed concern of infectious pathogens, such as hepatitis, being transferred via the newly invented Ped-O-Jet. The researchers reported two safety tests conducted upon the Ped-O-Jet:
1) A precipitin test was conducted after a Ped-O-Jet was used at five injection sessions, administering a total of 762 injections without replacing or cleansing of the nozzle. The researchers reported, “the results were negative, indicating the presence of less than 15 gammas of human serum, if any” (Benenson, 1959). For those of us who do not know, a gamma is an out-dated term for a unit of measurement. François Cardarelli (2003) explains in the Encyclopedia of Scientific Units, a gamma is a unit of measure of mass equal to one microgram (1µg). In doing the math, 15 micrograms converts to 0.015 microliters, or rather 15,000 picoliters. Therefore, based off of the principle that Hepatitis B is transmissible in around 10 picoliters and Hepatitis C is estimated to be ten times less infectious than Hepatitis B, this 15 gammas of human serum is capable of holding 1,500 hepatitis B particles and 150 hepatitis C particles. Upon further review, it could have been possible for serum hepatitis to have been transmitted in the amount of blood reported by WRAIR.
2) Possible transmission via the Ped-O-Jet was also assessed in a laboratory investigation. The researchers administered a saline injection with a Ped-O-Jet to a hog “at the peak of the viremia of hog cholera,” and then subsequently injecting a healthy hog. The results were unable to detect any contamination using the assays available during that era (Benenson, 1959; Weniger, Jones & Chen).
Based upon these investigations the researchers reported “no contamination” despite acknowledging “occasional bleeding” during Ped-O-Jet injections. Moreover, Benenson stated, “The problem of hepatitis has been minimized” (Benenson, 1959). He does not say the problem has been “eliminated” but “minimized.” Herein he acknowledges that transmission via the Ped-O-Jet was possible. However the science of the late 1950s could not detect contamination within such microscopic levels, and most importantly, no tests existed to detect viral hepatitis, which was still not well understood during this era.
- In 1977, the CDC’s Hepatitis Laboratories Division secretly conducted safety testing upon the Ped-O-Jet. CDC observed after firing of the Ped-O-Jet a drop of fluid remained on the nozzle orifice and would be sucked-back into the gun. Further tests to evaluate cross-contamination found once the Ped-O-Jet became contaminated it remained contaminated for the next two consecutive shots. Putting this into perspective, for every bleeder in the vaccination line the two subsequent persons were potentially exposed to blood. In vivo tests utilizing blood detection and HBsAg assays viable in 1977 upon two chimpanzees failed to demonstrate any cross-contamination. Although newer, more sensitive assays can detect HBsAg in dilutions literally 1,000 times smaller than the methods used within this experiment.. In 1977, the CDC concluded, “A more definitive statement regarding the safety of jet injector guns with regard to hepatitis B transmission is dependent upon specifically designed prospective seroepidemiologic studies” (CDC, 1977). CDC’s Unpublished Jet Injector Studies – Part 1
Numerous laboratory studies and field trials have implicated Ped-O-Jet injectors in cross-contamination of blood, Hepatitis B surface antigen, and other markers.
- In 1993-94, the CDC retested the safety of the Ped-O-Jet. CDC’s Animal and Mathematical Models both demonstrated Ped-O-Jet injectors posed a risk in the transmission of blood-borne pathogens. The results also indicated wiping the nozzle only reduced and did not eliminate the risk. The evaluation showed sufficient levels of contamination to prompt these CDC researchers to restrict the use of multi-use nozzle jet injector devices (Grabowsky et al., 1994). Part 3 – CDC Retests the Safety of Jet Injectors in 1993-94 The researchers stated,
They [jet injectors] should be avoided in some high risk groups or where proper cleaning and handling cannot be guaranteed. To reduce the risk of HBV or HIV transmission, the jet injector nozzle should be wiped after each injection with a rapidly drying agent (e.g., acetone). Use of a jet injector visibly contaminated with blood should be avoided (Grabowsky et al., 1994 [abstract]).
- In 1994, de Souza Brito reported on the risk of HIV and HBV transmission via the Ped-O-Jet injector while performing a routine mass vaccination campaign in 1991 to 2885 Brazilians. The researchers observed amongst three vaccination sites the percent of vaccinees who bled immediately after the Ped-O-Jet was removed ranged from 2.2 to 23.3 percent. The average percent of bleeders was 3.6 percent (104 out of 2885). The researchers found “instantaneous bleeding took place after injection in a significant proportion of cases and that there was therefore a risk of downstream infection of subsequent subjects” (WHO, 1998).
The presence of blood prompted researchers to asses the possibility of cross-contamination. The subsequent shot after administering a vaccination was fired into a vial and analyzed. Amongst the three vaccination sites results detected blood within 0.2 to 6.6 percent of the ejectates, with the average being one percent (28 cases out of 2885 vaccinees).
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). This finding is significant. There was no visible bleeding at the injection site in 27 out of 28 of the ejectates which contained blood, indicating blood transferred within microscopic levels not visible to the human eye.
However, as Dr. Martin Friede of the World Health Organization pointed-out, “volunteers were injected and then the next shot was put into a tube. And they were using the forensic occult blood detection stripes which measure about 2,000 picoliters as limit of detection. And in roughly one percent of the ejectates, blood was detected…so already at 2,000 picoliters, one percent of the ejectates did have blood in them” (FDA, 2005). The method of blood detection failed to detect blood within levels lower than 2,000 picoliters. HBV is detectable within 10 picoliters and HCV is estimated around 100 picoliters. Therefore, it is likely if a better method of blood detection were used, thus increasing the threshold to smaller than 2,000 picoliters, the results would have shown a larger percentage blood within the ejectates and more than one percent of the ejectates would have tested positive.
This study was significant in raising safety concerns of jet injectors amongst the World Health Organization and the Centers for Disease Control and Prevention.
- At the request of the World Health Organization, Dr. Peter Hoffman, from the United Kingdom’s Public Health Laboratory Service, created a model to detect whether low volumes of blood were being transferred via jet injectors. Amongst the brands Hoffman and his colleagues tested was the Am-O-Jet, which was a Ped-O-Jet marketed under a new name and owner (American Jet Injector; Weniger & Papania, 2008). Assessment of the Am-O-Jet / Ped-O-Jet device found a 34.2 percent contamination rate above 10 picoliters of blood and a 16.6 percent contamination rate above 50 picoliters of blood (Hoffman et al., 2001). These rates are sufficient to transmit blood-borne pathogens.
Hoffman reported the use of the ELISA caused underestimates of contamination. “We estimate…losses of analyte of around 30 – 50 %, and so our results are underestimates of blood contamination” (Hoffman et al., 2001).
- During the 1990s, the Program for Appropriate Technology in Health (PATH), conducted an unpublished in vitro study to assess the degree of contamination upon the Ped-O-Jet nozzle. The tests sought to detect contamination in three areas: 1) On the surface of the skin that was injected, 2) in down-stream inoculations between patients, and 3) upon the surfaces of the jet injector that had contact with skin. Contaminants were tested to a sensitivity level of one picoliter, or rather 10-6 milliliter. “Although these tests were not as sensitive as the PHLS tests [by Hoffman], they showed systematic contamination of both the ejectate and the internal fluid pathway.” That is to say there was enough blood to contain a blood-borne pathogen in both the ejectate (i.e., the dose the next vaccinee would receive) and within the jet injector. PATH found, “a correlation between the extent of contamination and the level of back-pressure in simulated skin models” (WHO, 1997).
- Sweat and colleagues (2000) replicated and extended Hoffman’s study by testing the potential of cross-contamination of the Am-O-Jet / Ped-O-Jet device amongst calves and pigs. This study replicated all of the previous in vivo jet injector studies. “We have detected contamination well above currently [sic] levels that we would consider indeterminate or uninterpretable,” said Dr. Bruce Weniger, a coauthor of this study (FDA, 1999). In other words, the researchers found the rates of contamination were significant.
Of particular note within this study is the omission to a redesigned check-valve (Sweat et al., 2000). Previously the check-valve had been implicated in causing suck-back of fluid, thus allowing fluid or blood upon the nozzle to be sucked-back into the orifice. This undesirable phenomenon was documented in CDC’s 1977 investigation of the Ped-O-Jet. The redesign of the check-valve further implicates the inherent design faults of previous Ped-O-Jet models.
- In October of 1998, a collaboration between WHO, the Brazilian Ministry of Health and UK’s Public Health Laboratory Service conducted a field trial to assess the safety of the jet injectors. “At the request of the World Health Organization, a laboratory protocol of jet injection safety was developed that could test the capacity of jet injectors to transmit blood between injection recipients” (Hoffman et al., unpublished). In this study, human volunteers infected with Hepatitis B and Hepatitis C were injected with a saline solution by a Ped-O-Jet injector. The Ped-O-Jet then administered an injection into three test tubes. The ejectates were tested using ELISA. Contamination was defined as detection of more than 10 picoliters of blood. Researchers also tested if wiping of the nozzle with a cotton swab soaked in alcohol would reduce the degree of contamination within the ejectates. Dr. Martin Friede of the World Health Organization stated, “whether it was wiping with the nozzle or wiping without the nozzle, we had between 7 and 11 percent of the ejectates contaminated with blood” (FDA, 2005).The most shocking part of the results was in 14 of the 29 samples, there was no visible bleeding at the injection site. This means that cross-contamination of blood occurred within microscopic levels not visible to the human eye; of which 11 samples were from the first shot after the Ped-O-Jet became contaminated and 3 samples were within the second shot after the Ped-O-Jet became contaminated. The researchers stated, “Blood contamination did not seem to correlate with the rapidity or profundity of bleeding at the injection site, nor with individual injectors used.” Whether there was or was not any visible bleeding was irrelevant to cross-contamination (Hoffman et al., unpublished).
- In 2003-2004 PATH compared the safety of a protector cap needle-free injector (PCNFI) to the Ped-O-Jet by using a fluorescein test. For this experiment, each of the injectors administered an injection into a test model containing a fluorescein dye, followed by administering an injection into a test tube. Any fluorescein within the test tube would be evidence of cross-contamination via the jet injector. The threshold for contamination was defined as detection of more than 10 picoliters within the 0.5 cc sample. Results of the Ped-O-Jet found 75 out of 100 (75%) samples contained more than 10 picoliters of fluorescein (Zehrung, 2004).
After attending a CDC/WHO conference on jet injector safety in March of 2004, PATH altered the threshold of contamination from 10 picoliters to 0.04 picoliters. Members of the conference were in agreement that quantities smaller than 10 picoliters could be infectious (FDA, 2005).
PATH conducted the fluorescein test a second time using the new 0.04 picoliter threshold. Darin Zehrung, the Associate Technical Officer at PATH, explained the results of the experiment in detail at a 2005 FDA conference on jet injector safety. Mr. Zehrung presented images which demonstrated the Ped-O-Jet as well as the injection site were both contaminated with fluorescein dye. This is known as splash-back. Results of the Ped-O-Jet found contamination in 100 out of 100 (100%) of the ejectates. The average volume of fluorescein contamination within the ejectates was 268 picoliters. The tests demonstrated cross-contamination with the Ped-O-Jet. No contamination was found with the PCNFI (FDA, 2005).
Studies suspect Ped-O-Jet injectors for the high prevalence of blood-borne pathogens.
- In 1996, during one of the most severe meningococcal meningitis outbreaks in the history of Nigeria, health officials were forced to use Ped-O-Jet injectors due to a shortage of syringes and needles. The official report of the mass vaccination campaign by Mohammed and colleagues (2000) stated,
An important problem of mass vaccination in Africa is the inadequate supply of syringes and needles, necessitating the use of ‘Ped-O-Jet’ injectors for vaccination, as happened during this epidemic. We may never know how many infectious agents (including hepatitis B and C viruses and HIV) were transmitted as a result of using these injectors, but clearly their use must be stopped as soon as practicable.
- Mboto and colleagues (2013) could not rule-out jet injectors as a possible source for the high prevalence of Hepatitis C in South Nigeria.
Iatrogenic medical or dental exposure including the use of improperly sterilized medical or dental equipment, reused needles or syringes, hemodialysis equipment, oral hygiene instruments, and jet air guns have all been associated with the transmission of HCV. However, these parameters were not evaluated in this study. Their contributory role in the transmission of HCV in this region cannot be down placed taking into consideration the poor health infrastructures that exist in the country (Mboto et al., 2013).
An association between Ped-O-Jet injectors and Hepatitis B was found using statistical modeling.
- In 2001, Souto and colleagues performed a multi-variant analysis to evaluate the risk factors for transmission of the hepatitis B virus. Out of 754 participants from a town in the Amazon basin of Brazil hepatitis B infection was found in 232 individuals (31%), with 19 individuals (3%) testing HBsAg positive. The multi-variate analysis found receiving a yellow fever vaccination with a Ped-O-Jet injector was a risk factor for acquiring hepatitis B (Souto et al., 2001). Dr. Shewit Bezabeh, a Medical Officer at the FDA, stated at a 2005 conference, Souto’s multi-variant anyalsis “implicat[es] the device as a vector for disease transmission” (FDA, 2005).
An association between Ped-O-Jet injectors and Hepatitis C was found within several epidemiological studies.
- An epidemiological study in Lahore, Pakistan found an association between Hepatitis C and the Smallpox Eradication Campaign. Results of the study found,
There was a significantly higher likelihood of hepatitis C antibody seroprevalence in individuals vaccinated for smallpox versus nonvaccinated individuals (21.0% vs. 4.6%, P < 0.001, age-adjusted odds ratio, 3.39; 95% confidence interval, 1.36-8.46)…Following adjustment for age, sex, and history of other conditions, including transfusion, the association between prior smallpox vaccination and hepatitis C antibody seroprevalence remained strong and highly significant (multivariate adjusted odds ratio, 6.11; 95% confidence interval, 2.58-14.51)” (Aslam et al., 2005).
Aslam and colleagues concluded, “These results suggest that the widespread prevalence of hepatitis C infection in Pakistan may be an unintended consequence of the country’s smallpox vaccination program and that blood transfusion is also a significant risk factor” (Aslam et al., 2005).
Use of Ped-O-Jet injectors in Pakistan’s smallpox eradication campaign has been documented. “WHO provided some l00 jet injectors to the national programmes in Pakistan, the Sudan and Zaire.” From 1969 to 1970, a mass vaccination campaign was conducted in the Punjab Province of Pakistan, in which 25,600,000 smallpox vaccinations were administered. The city of Lahore, the locale of Aslam’s study, is the capitol of Punjab Province (Fenner et al., 1988).
- Ivantes, Silva & Messias-Reason (2010) conducted a cross-sectional survey on the prevalence of hepatitis C antibodies in Tamboara, Brazil. In assessing the risk factors of 816 residents, vaccinations with Ped-O-Jet injectors were found to be a significant risk factor.
The authorities responsible for health care in Tamboara had a hypothesis that the high prevalence of anti-HCV was related with jet injection devices. Up to 1990, vaccination with this technique was used especially for prevention of yellow fever in Brazil. An epidemiological survey by Souto et al. in a Center-West Brazilian city suggests that the jet injection device has facilitated hepatitis B contamination in the population. In this study, some healthcare procedures related to anti-HCV transmission were identified by univariate analysis. Injections with glass syringe, vaccination with jet injection devices and blood transfusion before 1993 were significant risk factors (emphasis added).
By univariate analysis, the significant risk factors for HCV infection were as follow: familial history of hepatitis (p = 0.04), injection with glass syringe (p < 0.001), vaccination with jet (needle-free) injection devices (p = 0.034)…(emphasis adeded) (Ivantes, Silva & Messias-Reason, 2010).
- A study of 526 Vietnam-era veterans with Hepatitis C implicated the military’s Ped-O-Jet injectors as a risk factor. The researchers, Boscarino and colleagues (2014), had patients fill-out questionnaires to identify Hepatitis C risk factors. “Among veterans reporting ‘other’ exposures, the reason for this was primarily due to veterans reporting exposure to vaccinations or shots in the military.” Boscarino further stated,
Vaccinations in the military during the Vietnam War era were often done with pneumatic air-guns, en masse, during military induction and prior to overseas deployments. Typically, service members received multiple injections as they moved through these vaccination lines. Given this vaccination method, it was not uncommon for veterans to be bleeding by the time they reached the end of the line.
Boscarino added, “it is noteworthy that neither history of drug abuse treatment nor history of injection drug use was associated with Vietnam era veteran status…studies related to the prevalence of risk factors for HCV among veterans may be biased [hence, referring to VA’s HCV studies]” (Boscarino et al., 2014).
These studies demonstrate that the Ped-O-Jet was as fallible as any other jet injector. The studies prove cross-contamination of relevant volumes of blood via Ped-O-Jet injectors is more than just theoretically possible but scientifically proven. Moreover, epidemiologically studies have implicated Ped-O-Jet injectors in the transmission of Hepatitis C.
- (American Jet Injector) American Jet Injector, Lansdale, PA; 19446-4520, USA; email@example.com (the Am-O-Jet™ is an exact design of the out-of-patent Ped-O-Jet® device).
- (Aslam et al., 2005) Aslam M, Aslam J, Mitchell BD, Munir KM. “Association Between Smallpox Vaccination and Hepatitis C Antibody Positive Serology in Pakistan Volunteers.” Journal of Clinical Gastroenterology. 2005 Mar;39(3):243-6.
- (Benenson, 1959) Benenson AS. Mass immunization by jet injection. In: Proceedings of the International Symposium of Immunology, Opatija, Yugoslavia, 28 September – 1 October 1959 (International Committee for Microbiological Standardization, Secton of the International Association of Microbiological Societies). Zagreb: Tiskara Izdavackog zavoda Jugoslavenske akademije, 1959, pp. 393-399 [Library of Congress Classification: QW 504 I60p 1959].
- (Boscarino et al., 2014) Boscarino JA, Sitarik A, Gordon SC, Rupp LB, Nerenz DR, Vijayadeva V, Schmidt MA, Henkle E, Lu M. Risk factors for hepatitis C infection among Vietnam era veterans versus nonveterans: results from the chronic hepatitis cohort study (CHeCS). J Community Health. 29 March 2014.
- (Cardarelli, 2003) Cardarelli François(2003). Encyclopedia of Scientific Units, Weights and Measures. Springer-Verlag London Ltd. ISBN 978-1-4471-1122-1.
- (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).
- (FDA, 1999) Food and Drug Administration. General Hospital & Personal Use Devices panel: open session. Department of Health and Human Services Meeting. Rockville, MD. 2 August 1999.
- (FDA, 2005) FDA. General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee. August 9, 2005. 35th Conference. Washington, D.C.
- (Fenner et al., 1988) Fenner F, Henderson DA, Arita I, Je〉ek Z, Ladnyi ID. Smallpox and its Eradication, Geneva: World Health Organization, 1988 (ISBN 92 4 156110 6).Available at: http://www.who.int/smallpox/9241561106.pdf.
- (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.
- (Grabowsky et al., 1994 [abstract]) 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 [abstract]. 1994.
- (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 immunization. Vaccine 19 (2001): 4020-4027.
- (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).
- (Ivantes, Silva & Messias-Reason, 2010) Ivantes PC, Silva D & I Messias-Reason. “High Prevalence of Hepatitis C Associated with Familial History of Hepatitis in a Small Town in South Brazil. Efficiency of the Rapid Test for Epidemiological Survey.” Brazil Journal of Infectious Disease 2010;14(5):483-488.
- (Mboto et al., 2013) Mboto CI, Asikong BE, Lennox J, Lawson UD. Hepatitis C Virus Prevalence Rate and Risk Factors in Jaundice and Non-Jaundice In-patients Seen in Two Tertiary Health Facilities in South Nigeria. J. Microbiol. Biotech. Res., 20013; 3(4): 1-6.
- (Mohammed et al., 2000) Mohammed I, Abdussalam N, Alkali AS, Garbati MA, Ajayi-Obe EK, Audu KA, Usman A, Abdullahi S. A Severe Epidemic of Meningococcal Meningitis in Nigeria, 1996. Royal Society of Tropical Medicine and Hygiene, 2000 (94): 265-270.
- (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.
- (Weniger, Jones & Chen) Weniger BC, Jones TS, & Chen RT. The Unintended Consequences of Vaccine Delivery Devices Used to Eradicate Smallpox: Lessons for Evaluating Future Vaccination Methods.
- (Weniger & Papania, 2008) Weniger BG, Papania MJ. Alternative Vaccine Delivery Methods [Chapter 61]. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines, 5th ed. Philadelphia, PA: Saunders (Elsevier); 2008;1357-1392.
- (WHO, 1997) World Health Organization. Steering group on the development of jet injection for immunization. May 14, 1997. [draft]
- (WHO, 1998) World Health Organization. Technet Consultation. Expanded Programme on Immunization. Conference 16-20 March 1998. Copenhagen. WHO/EPI/LHIS/98.05.
- (Zehrung, 2004) Zehrung D. Jet Inject for Mass Immunization: Design Update and Safety Testing Strategy. Presentation for Global Vaccine Research Forum. 10 June 2004.