Coxiella burnetii
In each example which level applies is marked with colour and with (A).
Those with more information and notes can be found in the accordion below each section (Technical feasibility, Public Health value, time scale and cost of development). They are marked with the notepen 
icon.
| Criterion | Low feasibility | Medium feasibility | High feasibility |
|---|---|---|---|
| Provenance of pathogen | No understanding of provenance | Some understanding of provenance, with limited understanding of epidemiology | Known disease, with well understood epidemiology (A) |
| Similarity to known pathogen | Dissimilar, at least in initial analysis, to any known pathogen | From a known family of pathogens | Closely related to a well characterized pathogen (A) |
| Can the pathogen be cultured in a laboratory | Very difficult to culture | Possible to culture, but lengthy and difficult process (A) |
Can be cultured |
| Complexity and size of pathogen | Large and complex pathogen | Medium sized pathogen | Small and simple pathogen (A) |
| Antigenic diversity | High genetic diversity, with high mutation rate and lack of annotated genomic data | Some genetic diversity with moderate mutation rate | Little genetic diversity, with low mutation rate. Large amounts of well annotated genomic data available (A) |
| Biomarkers for safety/efficacy | No understanding of biomarkers for safety or efficacy | Some understanding of biomarkers that may relate to safety/efficacy | Clear understanding of biomarkers for both safety and efficacy (A) |
| Host-immune response | No known cases of natural immunity, and pathogen is immune modulatory | Some cases of natural immunity, but unclear whether this is durable and protective. Pathogen is generally perceived as not being immune modulatory | Cases of natural immunity which are both durable and protective, pathogen is not immune modulatory, and neutralising antibodies are protective (A) |
| Available model organisms, including human challenge models | Lack of suitable animal model, and/or suitable human challenge model | Suitable animal model and/or suitable human challenge model may require some development | Suitable animal model, and/or suitable human challenge model is available (A) |
Coxiella burnetii is the causative agent of Q fever. The primary reservoirs are ruminants such as cattle, sheep and goats. Infections in humans is often asymptomatic but acute or chronic disease can occur. In pregnant women the disease can cause still births, abortions and premature births. Human infection is mostly through the aerosol route, via the inhalation of soils contaminated with fluids from an infected animal. Epidemiology and disease presentation are described. In this category, vaccine production against this organism should be considered highly feasible.
Coxiella burnetii is a Gram negative obligate intracellular pathogen. It belongs to the γ subdivision of the proteobacteria. It is a member of the Rickettsiae family including Ehrlichia and Rickettsiae and Orientia, found in ticks, lice, fleas, mites and mammals and all are considered potential zoonotic pathogens.
Coxiella burnetii has been considered difficult to culture for several years due to an absolute requirement for growth within eukaryotic cells. This has significantly hampered the development of genetic tools for manipulating the organism. However, a medium that supports axenic growth has recently been developed, making laboratory culture of this bacterium more amenable. Medium/High feasibility.
The genome of Coxiella burnetii is about 2.2 Mb containing approximately 2,400 genes. This genome size is relatively small when compared to other bacterial genomes sequenced to date.
To score as highly feasible. The organism should have little genetic diversity with low mutation rate. Alternatively, large amounts of genomic data should be available. Studies indicate that there is a lack of broad genetic variance in Coxiella burnetii. This fits with the organism’s obligate intracellular lifestyle that limits opportunities for genetic exchange. It seems that the organism is in fact undergoing reductive evolution and undergoing genome downsizing to potentially further specialise for its intracellular lifestyle. Several Coxiella burnetii genome sequences are available although the first sequence from a human isolated strain was only published in 2015. In this category a Coxiella burnetii vaccine scores as highly feasible.
Several human vaccine trials have been carried out against Coxiella burnetii, therefore markers for vaccine safety and efficacy are established. In addition, studies have been published reporting that antibody responses have been characterised in vaccinated as well as acute and chronic Q fever sufferers
In order for a vaccine to be assembled against a particular organism, there should be reported cases of natural immunity that is both protective and durable. The pathogen must not be immunomodulatory and neutralising antibodies must be protective. Coxiella burnetii infection in humans causes Q fever, this is typified by symptoms such as pneumonia, fever, headache and myalgia. In most cases patients recover and are immune to further infections by Coxiella burnetii. B cells have been demonstrated to play a critical role in vaccine-induced immunity to Coxiella burnetii by producing protective antibodies. The exact mechanism however, of protective immunity to Coxiella burnetii is not well understood. Overall a vaccine to prevent Q fever can be rated as Highly feasible based on these findings.
Several animal models for Coxiella burnetii infection have been utilised ranging from mice to non-human primates to both evaluate and characterise the organism and vaccines.
| Criterion | Low priority | Medium priority | High priority |
|---|---|---|---|
| Infectivity or rate of spread of pathogen |
Rapid spread with high attack rate | Moderate rate of spread and attack rate | Pathogen is poorly transmitted, spread is very slow, and attack rate is low |
| Case fatality rate/disability burden | Low case fatality rate/ disability burden | Moderate case fatality rate/disability burden (A) |
High case fatality rate/disability burden |
| Infectivity before symptom onset | Not infectious before the onset of symptoms | May be infectious before the onset of disease(A) | Highly infectious before disease onset(A) |
| Environmental factors | Environmental factors are easily modulated | Moderately difficult to address environmental factors | Environmental factors cannot be modulated (A) |
| Geographical spread | Small isolated pockets of disease | Moderately spread | Large disseminated disease outbreak (A) |
| Target population | Lack of clarity on target population, with the level of prevention that is acceptable/desirable unclear | Some clarity on target population and level of prevention desirable | Clarity on target population and level of prevention desirable (A) |
| Availability of potential alternatives to vaccination | There are good alternatives to vaccination currently available which can be rapidly deployed to control the disease outbreak | Effective alternatives to vaccination could be rapidly developed | Effective alternatives to vaccination are not currently available and are not on the horizon (A) |
For a pathogen to be considered high priority in this category it should be poorly transmitted with very slow rate of spread and low attack rate.
The largest ever reported outbreak of Q fever occurred in the Netherlands between 2007-2010 and resulted in more than 3,500 Q fever cases. It should be noted that this organism is considered a zoonotic pathogen with global distribution. Combine this with the high potential for aerosol spread due to the very low infectious dose (10 or fewer organisms) required to potentially cause illness. Reports of high attack rates have been published so the organism could be considered low priority.
In this category notice that under low priority are organisms that have rapid spread and attack rates, one must point out that this is indicated with the caveat that such organisms should be considered low priority unless there is potential to prevent a pandemic by vaccinating populations outside of the affected country. Potential Q fever pandemics could be prevented by such means, therefore the pathogen should actually be classified as high priority.
Q fever presents itself as a flu-like illness. At times pneumonia and hepatitis can present. A minority of patients are unable to clear the bacteria and develop a chronic infection that often presents as endocarditis (60-70% of chronic infections). The CDC estimates that the rate of hospitalisation among Q fever cases is around 50%. The estimated case fatality rate is less than 2 % of hospitalised patients. Chronic Q fever occurs in about 5% of acutely infected patients and the case fatality rate in untreated patients with endocartidis ranges from 25-60%. Patients with endocariditis require at least 18 months of antibiotic treatment for a successful outcome.
10 to 25% of acutely infected patients suffer from post-Q fever fatigue syndrome. This is characterised by pain in muscles and joints, severe headaches, night sweats and fatigue.
In this category Coxiella burnetii vaccine development should be considered as medium priority.
Person to person transmission of Coxiella burnetii is very rare. In fact this appears as controversial. Developing a vaccine to prevent Q fever should be considered as low priority. However, the risk of infection with this pathogen is not from person to person transmission but from infected animals. Considering this caveat, one should re-categorise the need to develop a vaccine as high priority.
Incubation period:
Incubation periods between 2-3 weeks are routinely reported for acute Q fever.
Chronic infection however may manifest between 6 weeks and several years subsequent to acute Q fever.
Due to this wide range of incubation periods, Coxiella burnetii could be categorised as medium/high priority.
These cannot be modulated in the case of Coxiella burnetii and as such vaccine development should be considered as high priority.
Coxiella burnetii is a globally distributed zoonotic pathogen and clearly there is potential for a large disseminated outbreak.
Coxiella burnetii is considered a potential biological warfare agent. The low aerosol infectious dose and varied animal reservoir does indicate that there is potential for infection irrespective of gender/age/health status. Based on these indication, a Coxiella burnetii vaccine should be considered as high priority. Under normal conditions, the most at risk populations is composed of those individuals who have regular contact with cattle, sheep, maintaining livestock, working in abattoirs or in rural areas.
Doxycycline is the treatment of choice for acute Q fever. Usual dosage indicated is 100 mg taken orally twice daily for 15-21 days. Chronic Q fever is much more difficult to treat and the recommended treatment is a combination of doxycycline and quinolone antibiotics often prescribed for years. Recently, doxycycline resistant clinical isolates have been described, and independent studies have described DNA gyrase mutants that render strains resistant to quinolones. As such vaccine development should be considered as high priority.
Time scale and cost of development
| Criterion | Low priority | Medium priority | High priority |
|---|---|---|---|
| Available vaccine candidate(s) | No vaccine in development and route map for getting to Phase I trials not yet developed | Promising candidates exist, and means of rapidly developing to Phase I can be identified | Suitable vaccine may be in late stages of development (A) |
There is no globally approved vaccine against Coxiella burnetii.