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Lessons Learnt from the 2017/2018 Plague Outbreak in Madagascar

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Lessons Learnt from the 2017/2018 Plague Outbreak in Madagascar Lessons learnt from the 2017/2018 plague outbreak in Madagascar Pr André SPIEGEL and Plague IPM Group Directeur de l’Institut Pasteur de Madagascar 29th European Society of Clinical Microbiology and Infectious Diseases Symposium Global health: African update ESCMIDAmsterdam, Netherlands eLibrary 3th-16th April 2019 © by author Plague Y pestis / rodents / fleas and… humans Rodents Humans and Secondary fleas Pneumonic form Yersinia Person to person transmission pestis Possible evolution to Flea Bubonic form Infected rodent ESCMID eLibrary 2 © by author Plague in Madagascar 1898 : introduction of the Plague in Madagascar (Toamasina) • 1898 : Toamasina epidemic • 24 november 1898 : 1th cas • 1921 : Antananarivo • Following the construction railways • Spread in Madagascar • Endemic to the present day ESCMID eLibrary 3 © by author Plague in Madagascar Rural / seasonal / bubonic • Endemic area • Rural areas of the Central highlands • Natural foci of plague • Altitude > 800 m ESCMID eLibrary 4 © by author Plague in Madagascar Rural / seasonal / bubonic : Reservoirs and Vectors (1) (1) (2) Urban coast Rural area C C (1) B B A A B B (2) Urban highland ESCMID(1) (2) eLibrary(1) A : Rattus rattus (1) : Xenopsylla cheopis B : Rattus norvegicus (2) : Synopsyllus fonquerniei 5 C : Suncus©murinus by author Plague in Madagascar Rural / seasonal / bubonic • Seasonal : October to April • Cases • 500 / year • Bubonic form predominant > 85% notified cases (1998 – 2016) 1998 - 2016 ESCMID eLibrary 6 (Andrianaivoarimanana© V et al,by EID 2019,25,220 -228)author Plague in Madagascar Biological diagnosis • Clinical suspected case or dead suspected case suspicion • Biological specimen: bubo, sputum, blood • 3 biologics tests • Rapid Diagnosis Test : AgF1 (RDT-F1) • Molecular biology: cPCR and qPCR • Bacteria : Culture (antibiotic resistance) • Strategy • Health facility : TDR ESCMID• Institut Pasteur de Madagascar : TDR,eLibraryPCR (RTPCR), Culture 7 © by author Plague in Madagascar Definitions (WHO 2006) • Suspected case • All clinically-suspected plague cases that meet the clinical and epidemiological criteria as per WHO recommendations • Probable case • Clinically-suspected cases, with • RDT + or • PCR + • Confirmed case • Clinically-suspected cases, with • Culture + or ESCMID• RDT + and PCR + eLibrary 8 © by author Plague in Madagascar Alert : 11 September 2017 • Toamasina • Health car worker • Cough, fever • Admitted : 10/09 • Deceased : 11/09 • Phone investigation • Contact with patient • Unknown disease ESCMID• Rapidly deceased eLibrary 9 © by author Plague outbreak, Madagascar 2017 Investigation : index case ANKAZOBE 26/08 90 km Ankazobe Toamasina Antananarivo Male, 31 years Moramanga Ankazobe 25/08 : first signs ANTANANARIVO 27/08 100 km 28/08 ESCMIDMORAMANGA eLibrary100 km TOAMASINA 10 © by author Plague outbreak, Madagascar 2017 Investigation : index case (contacts in taxi-bus) Vohémar 2 1 Funeral was Toamasina Antananarivo 1 carried at 3 Toamasina 30/08/2017 2 3 Male, 26 yrs, student Native of Vohémar Male, 3 yrs Contacts in the taxi- 01/09 : first signs Native of Antananarivo bus to Toamasina : 02/09 : Death in Toamasina 30/08 : first signs Interhuman transmission No treatment 02/09 : hosp :Toamasina 03/09 : Death ESCMIDThe body Antananarivo (car) NoeLibrary treatment Vohémar (plane) After a death watch the body transported to Antananarivo by 11 © by authorcar on 04/09 Plague outbreak, Madagascar 2017 Investigation : the beginning Index case 1 2 2 cases in 1 case in Mahajanga Vohémar 3 5 1 case in 9 cases in Toamasina which 2 deaths Tsiroanomandidy Respiratory distress evolved 4 1 case in Analavory rapidly to death 6 Source: Géomatique, Epidémiologie, IPM. ESCMID11 cases in Faratsiho which 1 death (E) eLibrary Succession of deaths in same family in Antananarivo alerted health workers on 12 ©11/09/2017. by author Plague outbreak, Madagascar 2017 Investigation : 27/08 au 15/09 From 27/08 to 15/09 7 deaths 24 cases In 8 health districts Vohémar Mahajanga 1 case Source of outbreak Ankazobe : plague area ANKAZOBE Index case Extension to : • Toamasina Analavory 1 case Toamasina • non endemic plague area Antananarivo • Main commercial seaport • 206,000 hab Tsiroanomandidy 1 case • Antananarivo Faratsiho • Capital • High population density • 24 cases ESCMIDNotification eLibrary to WOH 13/09 according to IHR 13 © by author Plague outbreak, Madagascar 2017 1th Aug to 26 Nov 2017: 2,417 reported cases • 1,878 (78%) PP • 395 (16%) PB Alert • 1 septicemic • 140 unspecified Alert ESCMID eLibrary Daily number of notified plague cases by case classification 14 (Randremanana© Ret al, Lancet infecbyDis, 2019) author Plague outbreak, Madagascar 2017 1th Aug to 26 Nov 2017: 597 confirmed /probable cases 597 confirmed / probable (25%) 418 / 1,878 139 / 395 39 /140 (22%) (35%) (28%) Pneumonic Bubonic Unknown (32 confirmed) (32 confirmed) (6 confirmed) •ESCMIDSuspect: clinical presentation + epid eLibrary. context • Probable: RDT + or PCR + • Confirmed: (RDT + and PCR +) or (culture +) 15 © by author Plague outbreak, Madagascar 2017 1th Aug to 26 Nov 2017: cases geographical distribution 69% of PP in Antananarivo and 15% in Toamasina Pneumonic Bubonic ESCMID eLibrary 16 © by author Plague outbreak, Madagascar 2017 1th Aug to 26 Nov 2017: clinical signs and CFR • Pneumonic (confirmed) • Median age : 26 years • Male : 72% • 25% used antibiotic before examination • Clinical : cough (81%) fever (75%) chest pain (50%) hemoptysis (48%) • CFR : 25% (probable 8%; suspected 5%) • Bubonic (confirmed) suspected 2% CFR • Median age : 15 years probable 6% Bubonic • Male : 59% confirmed 24% • Clinical : adenopathy (100%) fever 98%) suspected 5% • CFR : 24% (probable 6%; suspected 2%) probable 8% • ESCMID eLibraryPneumonic confirmed 25% 0% 10% 20% 30% 17 © by author Plague outbreak, Madagascar 2017 Strains profiles • 50 Yersinia pestis strains isolated • 8 from PP, 41 from BP, 1 unspecified form) • All strains susceptible to tested antibiotics • 37 isolated strains sequenced • Close to the strains isolated in previous years in in endemic district • Including 8 strains of PP • All different • Important genetic diversity • 1 strain from a case epidemiologically linked to initial PP chain ESCMID• 4 of them associated with BP strains eLibrary 18 Source: Pasteur Institutes© Paris andby Madagascar. Submitted author for publication Plague outbreak, Madagascar 2017 National and international response • Malagasy high-level workgroup, chaired by the prime minister • Coordination health activities in collaboration with partners • WHO : very strong technical and operational support • GOARN • Mobilisation ressources : UK, France, USA • Institut Pasteur de Madagascar and Institut Pasteur (Paris) • USAID • International Federation of the Red Cross • MDM, MSF,……... ESCMID• Cost : $4 million to the response eLibrary 19 © by author Plague outbreak, Madagascar 2017 National and international response • Improvement of the surveillance, to detect and treat early • Case management and prevention of inter-human transmission • Social mobilization, health education • Control in the country and at the borders • Vector control and rat proofing ESCMID eLibrary 20 © by author Plague outbreak, Madagascar, 2017 Response : Case management / prevention person to person transmission Clinical suspicion Isolation if PP suspected Collection of clinical specimen + RDT Active finding of contacts + Chemoprophylaxis Presumptive treatment . Pneumonic plague : Streptomycin 8 days ESCMID eLibrary(= 40 IM) Desinfection of house . Bubonic plague : Streptomycin IM 3 days followed by Sulfamethoxazole- trimethoprim 5 days 21 © by author Plague outbreak, Madagascar 2017 Response : safe burial practices Funeral rites Funeral secured Death suspected ESCMIDActive finding of contacts eLibraryDesinfection of house + Chemoprophylaxis 22 © by author Plague outbreak, Madagascar 2017 Response : other measures • Social mobilization, health education • plague = shameful disease • Panic in the population and over reaction • Difficulties to managing rumors and panics • Control in the country and at the borders ESCMID eLibrary • Vector control and rat proofing 23 © by author Plague outbreak, 2017 Interpretation and experience feedback • Biological diagnostics: no gold standard diagnostic available • Culture • Very specific but no sensitive • Only 8 Y. Pestis strains isolated on PP • Quality of sputum samples ? Transport too long ? Antibiotic treatment before ? • Contamination by commensal flora of the upper respiratory tract • RDT • RDT performance on pneumonic plague samples had not been evaluated • Misuse / misinterpretation in non-endemic areas • PCR • Conventional pla PCR • Insufficient specificity pneumonic plague • PCR pla, inv1. ESCMID• Importance of molecular biology +++eLibrary 24 • Deployment© byof the mobile authorlaboratory Plague outbreak, 2017 Interpretation and experience feedback • High % of suspected cases (78%) • Pneumonic cases : 23% of notified cases are confirmed / probable • Frequent use of antibiotics • Misdiagnosis : new areas affected, lack of clinical experience • Large number of suspected cases • major hurdle for logistical management of different aspects of the response • Need to change 2006 WHO classification cases • suspect cases with all lab results negative "non-cases“ ESCMID eLibrary 25 © by author Plague outbreak, 2017 Interpretation and experience feedback • Case management response • Urban context made complex the implementation of usual control measures • 7289 contacts • Change treatment : streptomycine
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