Category Archives: Africa

Ebola’s Chain of Infection

Chain of Infection A chain of infection is a method for organizing the basic information needed to respond to an epidemic.  I’ve gathered the best information I’ve been able to find. As the current epidemic is analyzed, there is no doubt some of the recommendations and basic knowledge will change.

The Ebola Virus (EBOV)

img8The Ebola virus is a Filovirus, an enveloped RNA virus containing only eight genes. Three of the five ebola virus species are highly pathogenic to humans: Zaire ebolavirus (Case fatality rate (CFR) 70-90%), Sudan ebolavirus (CFR ~50%) and Bundibugyo ebolavirus (CFR 25%). The 2014 epidemic is caused by the  Zaire ebolavirus.

Ebola attaches to the host cell via glycoproteins that trigger absorption of the virus. Once inside the cell it uncoats and begins replicating the eight negative sense RNA genes (seven structural genes and one non-structural gene). It initially targets immune cells that respond to the site of infection; monocytes/macrophages carry it to lymph nodes and then the liver and spleen. It then spreads throughout the body producing a cytotoxic effect in all infected cells. Death occurs an average of 6-16 days after the onset of symptoms from multi-organ failure and hypotensive shock.

Symptoms present 2-21 days after infection and the patient is contagious from the onset of symptoms.  Symptoms include a fever, fatigue, headache, nausea and vomiting, abdominal pain, diarrhea, coughing, focal hemorrhaging of the skin and mucus membranes, skin rashes and disseminated intravascular coagulation (DIC). In the 2014 epidemic, abnormal bleeding has only occurred in 18% of cases and late in the disease process.

The Reservoir

Fruit bats in Africa are believed to be the primary reservoir. Transmission between bats and other animals is poorly understood.

ebola_ecology_800px

Portal of Exit

Ebola leaves its reservoir by contact with body fluids of an infected animal, often by bushmeat hunters. The spill-over is usually very small with the vast majority of human cases being caused by human to human transmission.

Transmission 

Transmission between humans occurs by contact of skin or mucus membranes with the body fluids of an infected person. Viral particles are found in all body fluids: blood, tears, saliva, sputum, breast milk,  diarrhea, vomit, urine, sweat and oil glands of the skin, and semen. Ebola can be found in semen three months after recovery from an infection but transmission by this route is poorly understood. Viral particles are found in other body fluids for 15 days or less after the onset of symptoms. It lasts the longest in convalescent semen and breast milk. All fluids from dead bodies are highly infectious.

All materials touched by the infected person, body fluids, medical waste, and used PPE must be discarded and destroyed as infectious medical waste. Non-disposable items like rubber boots, furniture, and building structures must be professionally decontaminated.

Ebola virus is a Biosafety Level 4 pathogen and a category A bioterrorism agent along with other viral hemorrhagic fevers.

Portal of Entry

Ebola enters the human body through breaks in the skin, including micro-abrasions and splashes on mucus membranes. Personal protective equipment (PPE) includes full body coverage including hood, mask or face shield, a tight fitting respirator, boots or shoe coverings, and double gloving. A buddy system should be used for dressing and disrobing. Removing PPE is a point of frequent contamination and should be done with help from another robed person.

Vulnerable populations

The most vulnerable populations for ebola are defined by their occupation. Care givers in medical facilities are at the highest risk because the viral titers reach the highest levels in fatal cases shortly before death. Mortuary and burial workers are also at high risk. The infectiousness of the bodies means that the usual burial practices can not be done in any setting or country. Home caregivers and decontamination workers would also be at a higher risk.

Information is lacking on survival vulnerabilities such as age, gender, pregnancy, or pre-existing conditions. More information on these aspects should be available in the post-epidemic analysis of the current epidemic.

 

References and further reading:

Martines, R. B., Ng, D. L., Greer, P. W., Rollin, P. E., & Zaki, S. R. (2014). Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg Viruses. The Journal of Pathology, n/a–n/a. doi:10.1002/path.4456 [in press]

Chowell, G., & Nishiura, H. (2014). Transmission dynamics and control of Ebola virus disease (EVD): a review. BMC Medicine, 12(1), 196. doi:10.1186/s12916-014-0196-0

Toner, E., Adalja, A., & Inglesby, T. (2014). A Primer on Ebola for Clinicians. Disaster Medicine and Public Health Preparedness, 1–5. doi:10.1017/dmp.2014.115

Bausch, D. G., Towner, J. S., Dowell, S. F., Kaducu, F., Lukwiya, M., Sanchez, A., et al. (2007). Assessment of the Risk of Ebola Virus Transmission from Bodily Fluids and Fomites. Journal of Infectious Diseases, 196(s2), S142–S147. doi:10.1086/520545

CDC: Ebola Virus Disease portal

Yersinia pestis found in human fleas, Madagascar 2013

Madagascar is consistently one of the top two countries in Africa (and usually the world) in cases of plague, caused by Yersinia pestis. For five years prior to January 2013, Madagascar registered 312 to 648 cases per year, with a majority being laboratory confirmed of which >80% were bubonic plague. Of the multiple reservoir species in Madagascar, the black rat (Rattus rattus) is the primary reservoir with Xenopsylla choepus being the main urban vector and Synopsyllus fonquerniei in rural areas.

After a nine case bubonic outbreak in the rural area of Soavina in the district of Ambatofinandrana (shown below), fleas were collected within and outside of five houses over three nights.


The team from the Institut Pasteur de Madagascar collected 319 fleas representing five genera; the most common being the human flea Pulex irritans (73.3%).  In this study, X. cheopis and S. fonquerniei were only collected outside of the houses. Pulex irritans was found only indoors where it made up 95.5% of flea species. Of the 274 fleas tested for Yersinia pestis, 9 pulex irritans were positive. These positive human fleas came from three homes, one of which had a confirmed case of human plague. None of the other flea species tested positive for plague.

Previous observations of pulex irritans in Madagascar suggest this flea may be responsible for domestic human-to-human transmission. High densities of human fleas were reported in plague outbreak villages in 2012-2013. Flea surveys on rats in Madagascar conducted over the last three quarters of a century show that pulex irritans are very rare on rats, suggesting it is not transmitting plague from rats to humans at least in Madagascar. Although pulex irritans are commonly called the human flea, they will feed on dogs and pigs  in addition to humans.  They have also been sporadically found on a variety of other mammals and birds, including rats.

Coping with human fleas as plague vectors will be a significant extra burden on the public health services of Madagascar. Ridding homes of human fleas can be a difficult task. It will however give plague researchers an opportunity to study pulex irritans as a vector in one of the top human plague producing countries in the world.

Within the last ten years, Madagascar has produced human plague cases from three different fleas and pneumonic transmission. With its diversity of plague reservoirs and now flea vectors, Madagascar is illustrating how deeply Yersinia pestis can penetrate and become entrenched in the environment.

Reference:

Ratovonjato J, Rajerison M, Rahelinirina S, Boyer S. “Yersinia pestis in Pulex irritans fleas during plague outbreak, Madagascar” [letter]. Emerging Infectious Disease. 2014 Aug [30 June 2014].http://dx.doi.org/10.3201/eid2008.130629

Wyrwa, J. 2011. “Pulex irritans” (On-line), Animal Diversity Web. Accessed July 01, 2014 at http://animaldiversity.ummz.umich.edu/accounts/Pulex_irritans/

Reactivation of Ancient Plague Foci in Libya, 2009

Landscape around Oran, Algeria,  and Tobruk, Lybia in 2009 that produced plague cases. (Cabanel et al, 2013)
Landscape around Oran, Algeria (2003), and Tobruk, Lybia (2009) that produced plague cases. (Cabanel et al, 2013)

Plague has been called a re-emerging disease primarily because cases have begun to appear in areas where plague has been absent for decades. Two recent surprising outbreaks occurred in Algeria, where plague had been absent for over 50 years, and in Libya after a 25 year absence. A team led by the Institut Pasteur explored possible relationships between the recent Libyan outbreak and the Algerian outbreaks. All of the information in this post comes from their report to be published in the February issue of Emerging Infectious Diseases (citation and link below).

The outbreaks under consideration were just south of Oran, Algeria in 2003, at Lanhouat, Algeria in 2008 and near Tobruk near the Libyan-Egyptian border in 2009. Another possible outbreak of plague occurred at Tobruk during the Libyan revolution in 2011.  Political unrest prevented a complete disease investigation of the 2011 Libyan epidemic. Past Libyan plague outbreaks have occurred from 1913-1920, 1972, 1976, 1977, and 1984. The largest outbreak in 1917 is credited with 1,449 deaths.

The 2009 Libyan index cases consisted of three children from one nomad family; one child died after two days of intensive care and the other two eventually recovered. Only one child had a tender cervical node. The other two, including the child who died, had signs of a severe infection but no visible buboes. The father reported having axillary lymphadenitis and a couple of sudden deaths in the region in the previous two months. A week after admission Libyan authorities reported 13 possible cases to the World Health Organization and requested assistance. The WHO-Libyan team identified two more women with painful inguinal nodes and “infectious syndrome”, but also concluded the initial estimate overstated the number of cases. There are five confirmed cases. The cases were spread 30-60 km from the index family’s home in Eltarsha, 30 km south of Toburk. Regional response included antibiotic treatment of contact persons, and insect and rodent control measures. No further cases were reported.

Diagnosis was confirmed by standard bacteriological assays and molecular characterization. All five confirmed cases were positive with the F1 antigen dipstick.  Yersinia pestis cultures were isolated from three patients,  all phenotyped to the Medievalis biovar by metabolic assays. Molecular characterization confirmed that all are the same Medievalis strain. Hybridization analysis indicates that it is most closely related to, but distinct from, strains isolated from Iranian Kurdistan in 1947 – 1951.

Using the same methods, the 2003 Algerian isolates were phenotyped to the Orientalis biovar. Molecular characterization confirmed that they are all related but not identical Orientalis strains. Activation of multiple related strains from an ancient foci in the same year suggests an environmental trigger. Comparing the 2003 strains to those isolated in 1944 and 1945 illustrate the complexities of plague foci. The 1944 isolate is a Orientalis strain that belongs to the same cluster of strains as the 2003 isolates and other strains from Morocco and Senegal.  The 1945 strain matched a molecular characterization of  Orientalis isolates from Saigon, Vietnam and is believed to have been transmitted by military transports during World War II.  Cabanel et al conclude that the 2003 Algerian outbreaks were caused by local Yersinia pestis strains. It should be noted that the third pandemic from the turn of the 20th century was a Orientalis biovar (1.Ori1).

Cabanel et al. note this is the only instance they could find of a Medievalis strain in Africa. The spread of cases over a 30-60 km region and isolation of related but different strains support the reactivation of an ancient plague focus. Unfortunately they did not have access to isolates from previous 20th century Libyan outbreaks (if they exist) that could have provided more certainty.

Reactivation of plague foci around the Mediterranean has been associated with climate change. They note that an unusually humid winter and good crops in Libya in 2009 favored rodent and flea abundance. Long dormancies may be part of Yersinia pestis’ natural history particularly in resource limited environments. This possibility will be one of the topics of my next post.

Cabanel et al. note that camel meat and livers have been associated with human plague cases in Libya (1976), Saudi Arabia (1994), Jordan (1997), and Afghanistan (2007). Additional local evidence suggested that the highly susceptible camels contracted the plague from local foci in these instances. Although camels do not survive plague long enough to transmit it very far, camel caravan routes may still have played a role in transmission if only by the other organisms also along the camel caravan route. Camels would have provided an abundant host to amplify the organism along the route. Camel fleas could have been carried among the cargo not unlike rat fleas in ship cargoes. Camel caravans would provide an ancient route for a Medievalis strain to reach Libya from the central Asia.

Reference

Cabanel, N., Leclercq, A., Chenal-Francisque, V., Annajar, B., Rajerison, M., Bekkhoucha, S., Bertherat, E., & Carniel, E. (2013). Plague Outbreak in Libya, 2009, Unrelated to Plague in Algeria Emerging Infectious Diseases, 19 (2), 230-236 DOI: 10.3201/eid1902.121031

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