Category Archives: Africa

A Synopsis of an Unusual Pneumonic Plague Outbreak in Madagascar, 2011

Plague appears in Madagascar every year, but it can still come as a surprise. It did in the January of 2011 when it appeared in an area of northern Madagascar that had never had an outbreak before. Not only was it a new area, but all of the cases were pneumonic. Not one case of bubonic plague. Eleven people were dead before antibiotics were given to the first patients on January 28. Vincent Richard and colleagues describe the outbreak in the forthcoming January issue of Emerging Infectious Diseases.

The index case was a thirteen year old boy who worked in a copper mine and developed a headache, fever and chills on a trip to his home village on January 6. He progressed to a fever, headache, a cough, severe chest pain and bloody sputum before dying at home on January 14. By January 22, his mother, her husband, daughter and granddaughter had died. Three other family members were showing symptoms of pneumonic plague when a neighboring family began to care for them beginning the second round of infections in twelve other people.  Visitors to the second household transmitted it to three more households. The last two fatal cases (19 & 20) were the brother who carried his sister to a traditional healer who was the last fatal case dying on February 9.

Plague transmission (Richard et al, 2015)
Plague transmission (Richard et al, 2015)

The epidemiological investigation identified 41 contacts: 17 from infected households and 25 who had more fleeting contact with a fatal case. None of these contacts had plague specific symptoms. All contacts were serum tested for plague with the Rapid Diagnostic Test (RDT, ‘the dipstick’) and all, but two who refused, were given prophylactic antibiotics. Details of how the contacts are connected are shown in the graphic above and narrated in the report by Richards et al in Emerging Infectious Diseases. Only two of these carriers were seropositive; one had a cough and refused antibiotics (c25) but did not progress. He is not considered a symptomatic case in the report. Three other contacts had mild pulmonary symptoms but were seronegative. They are not considered plague cases.  The wife of a fatal case cared for her husband and shared his bed until his death; she never turned seropositive.

Public health response followed the WHO protocols but was hampered by the outbreak being spread over seven villages 30 km from the index household in an area where plague had not been previously reported. This slowed the identification of contacts and dispensing antibiotics. Unfortunately postmortem specimens were not collected so there were only five specimens from symptomatic cases  to analyze. Initial sputum samples for three cases were positive for the Yersinia pestis F1 antigen by the RDT dipstick and all five specimens were transported about 900 km to the Institut Pasteur de Madagascar in Antananarivo to be analyzed. All attempts to culture Yersinia pestis from the specimens in bacterial media and mice failed.  Diagnoses were confirmed and titers quantitated by an ELISA based immunological detection for three cases. Cases were classified as suspected (17), presumptive (2) and confirmed (3) based on the WHO diagnostic criteria. The two presumptive cases were the seropositive non-symptomatic contacts. This highlights a problem with the WHO criteria since one seropositive case refused antibiotics and never developed plague specific symptoms. Presumptive should be a higher standard than suspected, which is based on clinical symptoms alone.

All cases that developed symptomatic pneumonic plague had the same symptoms: fever, chest pain, a cough, and bloody sputum. They were infectious for 48-72 hours after a 4-6 day latency period. This relatively long latency period allowed antibiotics to prevent the development of symptomatic plague in contacts. The effect of antibiotics on symptomatic patients was stark; five treated patients survived while all fifteen untreated patients died. With such a drastic difference between treated and untreated, the overall 75% case fatality rate is not really reflective of the virulence of the pathogen. Antibiotics alone determined the survival of symptomatic cases. Of the 36 people living in infected households, 20 developed symptomatic plague for an attack rate of 55% within the households; non-household contacts are excluded from the attack rate calculation.

Investigation of the presumptive focus is not begin until two months after the beginning of the plague response. Trapping of rodents in the area around the initial two villages,  Ambakirano and Ankatakata, produced 64 rodents and five dogs were sampled. Only one greater hedgehog (1 of 6) and two dogs were seropositive for Yersinia pestis by ELISA.  As wide ranging carnivores who are fairly resistant to plague, seroconversion in dogs is considered to be a good sentinel indicator. No fleas were collected; no dead rats were observed. All 51 black rats collected were seronegative, but Yersinia pestis DNA was isolated from the spleens of five rats. All strains fit the Malagasy specific 1.ORI3-k SNP pattern. There was enough minor variation in CRISPRs (a type of genetic fingerprinting information) to suggest a pre-existing enzootic focus is present. With such benign animal evidence, there is no reason to think that there was an epizootic that spilled over to humans. This is not surprising considering there were no bubonic cases. All of the human cases appear to be connected to the index case and to have passed human to human. Unfortunately, there is no mention of investigating a potential plague focus near the copper mine where the index case was working before symptoms appeared on his way to his home village.

While the survivors of the 2011 outbreak responded well to streptomycin, resistant strains were reported in the 2011 outbreak to Richards et al (2015) as personal communication. It is unclear if this means in an animal isolate from the region or another outbreak in 2011. Resistant strains have been reported in Madagascar since 1995 and are now apparently persistent.

This outbreak highlights how difficult it is to initially identify a pneumonic only outbreak. Spread by droplets, transmission can be broken by simple masks or, the Malagasy team suggests, even hygiene like turning away from others while coughing or covering the mouth and nose. People were able to care for and bury their dead without contracting disease.  On the other hand, antibiotics alone stopped the outbreak. Whether or not it would have ended on its own, we will never know. Although only two contacts were seropositive, prophylactic antibiotics likely prevented more infections.

References:

Richard V, Riehm JM, Herindrainy P, Soanandrasana R, Ratsitoharina M, Rakotomanana F, et al. Pneumonic plague outbreak, northern Madagascar, 2011. Emerg Infect Dis [Internet]. 2015 Jan [ahead of print publication 5 Dec 2014]. http://dx.doi.org/10.3201/eid2101.131828.

See my previous post for more information on antibiotic resistant Yersinia pestis in Madagascar.

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/