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.
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.
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.