Constância Ayres. Anticipating future emerging infectious diseases through collaborative research: a reflection on the Zika outbreak

Transcription

1 Roundtable Meeting on Zika Virus: Improving Detection, Preparedness, and Response, Through Surveillance and Research Anticipating future emerging infectious diseases through collaborative research: a reflection on the Zika outbreak Constância Ayres tans@cpqam.fiocruz.br

2 Vector control

3 Vector control Integrated control; Sustainable strategies; Permanent; Monitoring through surveillance; Choice of a good tool (sensitivity);

4 Quiescent eggs Dispersed Oviposition CICLO BIOLÓGICO 15 to 30 days Passive Dispersion

5 Biological traits of Aedes aegypti Highly antropophilic females; Monogamy (breeding can occur in 24 hours after emergence); Adapted to the urban environment (preference for premises); Prefer temporary breeding sites; Colonize reservoirs of potable water (>80% of breeding sites are inside houses).

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7 National Program for Dengue Control (PNCD)

8 PNCD components 1. Epidemiological surveillance 2. Vector control 3. Patients assistance 4. Integration of Agents (PACS/PSF) 5. Sanitation 6. Social mobilization and comunication 7. Training 8. Legislatioin 9. Social and political approach 10. Evaluation

9 Methods of control Focal treatment of breeding sites. Perifocal residual treatment of surfaces. Space spray -Ultra Low Volume spray.

10 Focal treatment (larvicides) Egg Temephos Bti Diflubenzuron Pyriproxifen Larvae Adult Pupae

11 Perifocal: Insecticide Residual Spraying (adulticides) strategic points

12 Use in the field - aplication PNCD guidelines: use of larvicide only when necessary Powder IPE

13 Space- Spray

14 Rede Nacional de Monitoramento - Morena Processo de avaliação para ingresso de dois novos laboratórios: 1. Medicina Tropical UnB 2. Universidade Federal do Paraná Laboratório de Entomologia/CE Laboratório de Entomologia CPqAM (Fiocruz/RJ) Regiões N NE SE S CO Laboratório de criação de Aedes aegypti Geraldo Magella Buralli/SP (*) Rede Nacional de Monitoramento de Aedes aegypti a Inseticidas

15 Temephos resistance in Brazil Chediak, M. et al., 2016

16 Aedes aegypti Histórico de Controle no Brasil Aedes aegypti control in Brazil Programa Nacional de Controle da Dengue- PNCD PNCD measures have not been enough to reduce Ae. aegypti populations, and consequently, to minimize the endemic-epidemic transmission of dengue, chikungunya and zika; Natural Ae. aegypti populations are highly resistant to chemical insecticide; Low coverage of larvicide control associated to: high percentage of closed premises/or refusal to inspection by the Health Agents (pendencies) and a high number of vacant lands;

17 Sites Real-Scale trials SMCP-Aedes Pernambuco - Northeastern Arid region 200 Km. Archipelago 500 Km Santa Cruz do Capibaribe Ipojuca Fernando de Noronha Island 87,538 inhabitants Area: km² 76,000 inhabitants Area: km²* 3,000 inhabitants Area: 17 km 2 (15 villages)

18 Mosquito surveillance Sentinel - Ovitrap Network Fixed sampling stations 262 Santa Cruz do Capibaribe 76 Ipojuca Centro 103 Fernando de Noronha The sentinel-ovitrap (S-Ovt) Period in the field: 30 days Containing Bti* SMCP-Aedes * Santos et al Field Evaluation of Ovitraps Consociated with Grass Infusion and Bacillus thuringiensis var. israelensis to determine Oviposition Rates of Aedes aegypti. Dengue Bulletin, 27: Araújo et al., 2007; Melo-Santos et al Long lasting persistence of Bacillus thuringiensis israelensis larvicidal activity in Aedes aegypti breeding sites. 18

19 Social Mobilization - Information SMCP-Aedes Public health authorities Technical staff of health services Community mobilization Vídeo FIOCRUZ 19

20 Information Flow SMCP-Aedes Egg collection Counting Data analysis Intervention Actions Planning Kernel Maps

21 Control-ovitrap (C-Ovt) Production SMCP-Aedes Non-Govermental Organization - ICRIAC collective ovitraps manufactoring * Regis et al Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian 21 Cities. PLoS ONE 8(7): e doi: /journal.pone

22 Egg Density Low High Kernel-Maps as decision support SMCP-Aedes Areas with high concentration of mosquito (hot spots). 22

23 Site infestation May 2008 Jan 2011 SMCP-Aedes POI: Positive Ovitrap Index EDI: Egg Density Index (Mean number of eggs/ovt-s/ 30 days) Santa Cruz** POI = 100% Ipojuca** POI = 92.6% Fernando de Noronha POI = 84% EDI = 1,597 eggs/trap/month EDI = eggs/trap/month EDI = 180,6 eggs/trap/month Infestation found after >10 years of temephos** or Bti treatments (6 cycles/year) PNCD. Araujo et al The susceptibility of Aedes aegypti populations displaying temephos resistance to Bacillus thuringiensis israelensis: a basis for management. Parasites & Vectors, v. 6, p , 2013.

24 SMCP-Aedes - Sensitivity to detect the A. aegypti presence SMCP-Aedes The system detects continuous mosquito oviposition in most sites. Egg laid = presence of blood fed Aedes females POI = 63 % 100 % House Index Santa Cruz = 3.8 to 12% Ipojuca = 0 to 0.8% Fernando de Noronha = 0 to 0.5% Index based on larval surveys are not sensible enough to revel the true level of infestation by A. aegypti * Regis et al Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian Cities. PLoS ONE 8(7): e doi: /journal.pone

25 After Control Before Control SMCP-Aedes Egg suppression >7,500,000 Egg density 90% in Santa Cruz 77% in Ipojuca Egg densities decreased progressively during the control intervention period, however the POI remained higher than 80%. * Regis et al Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian Cities. PLoS ONE 8(7): e doi: /journal.pone

26 Final Considerations SMCP-Aedes 16 The tools and strategies used in SMCP-Aedes allowed quantification of the active population of A. aegypti, indicating periods and places with high virus transmission risk. The strategy using control-ovitrap is cost-effective and compatible with other control measures. The methods and tools used motivated the assimilation of knowledge and encouraged social participation.

27 Surveillance will enable control programs to: Identify vectors; Evaluate the impact of vector control strategies; Management of insecticide resistance; Generate risk maps for exposure to arboviruses; Define priority areas for vector control; Predict outbreaks.

28 Why mosquito surveillance is important in SE Asia? Zika virus has been present in areas of Southeast Asia for many years, and several countries have reported occasional cases or small outbreaks of Zika virus infections. Zika virus is considered endemic in some countries, and a large number of local residents are likely to be immune; infections have occurred among travelers to Southeast Asia; Recent variations have been observed in the number of cases reported in Southeast Asia. This can reflect changes in awareness of Zika virus, surveillance and testing for Zika virus, or changes in intensity of Zika virus transmission. CDC

29 Aims: The surveillance efforts are focused on identifying arbovirus infections in mosquitoes as predictors of the potential risk of transmission to humans; to monitor the further expansion of the viruses; To provide base-line information for increment surveillance programs and initiating control activities in the event that ZIKV is introduced into the region.

30 May 2013 May 2014 Monitoring of Ae. aegypti in the City of Praia, Cape Verde by Positive Ovitrap Index (POI) for 2013 and 2014.

31 (Barnett, 1962) The incrimination of arthropods as vectors of disease Demonstration that members of the suspected population commonly feed upon vertebrate hosts of the pathogen; Demonstration of efficient transmission of the identifiable pathogen by the suspected vectors under controlled experimental conditions; Repeated demonstration that suspected vector collected under natural conditions, harbor the identifiable, infective stage of the pathogen; Demonstration of a convincing biological association in time and space between the suspected vectors and clinical or subclinical infections in vertebrate hosts.

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34 RT-qPCR results

35 Electronic Microscopy

36 ZIKV in salivary gland cell of Culex

37 ZIKV detected by FTA cards Ae. aegypti 10 6 Cx. quinquefasciatus 10 6 Ae. aegypti 10 4 Cx. quinquefasciatus 10 4

38 Field work Surveillance Diagnostic Analysis and Outcomes

39 Surveillance Field work material Collection Transportation Storage

40 Collection Aspiration indoor outdoor FTA cards Inactivate the virus RNA extraction

41 Transportation RNAlater alive

42 Registration

43 Vector infection is a rare event Need to increase the chance of detection Need to reduce the error Sampling proportionality

44 MIR Density

45 We need to take into account: Feeding behavior Number of bites mosquito/ person Collection Time period Sampling methods area Phase of outbreak Few human infections peak post-peak

46 the sampling process has to be adjusted to the most rare event MIR Considering ecological and biological factors Time of outbreak, habits

47 Vector ZIKV Infection Rate Local Aedes Culex MIR N Pools ZIKV+ Total Pools ZIKV+ Aedes Culex Recife-PE (2016) ,0 Vitória-ES Rio de Janeiro

48 Vector ZIKV Infection Rate Local Aedes Culex MIR N Pools ZIKV+ Total Pools ZIKV+ Aedes Culex Cabo Verde Mexico ,7 0 Malaysia ,78 - French Polynesia ,49 0 Micronesia (Yap) 41.2% % Gabon Senegal* *

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50 ZIKV Diagnostic

51 Direct and Indirect Laboratory Diagnostic Methods Nature Reviews Microbiology, S30-S37

52 Detection of ZIKV by RT-qPCR and RT-PCR

53 Bad!

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55 RT-qPCR Lanciotti, 2016

56 Primary x Secondary Flavivirus Infection

57 ZIKV Serology Summary

58 Other Samples? Urine Serum N=6 patients ZIKV RNA is detectable in urine at a higher load and with a longer duration than in serum

59 Other Samples? 182 patients ZIKV was more frequently detected in saliva compared to blood. The use of saliva sample increased the rate of molecular detection of ZIKV at the acute phase of the disease but did NOT enlarge the window of detection of ZIKV RNA.

60 ZIKV in Semen In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia. Eight weeks after first signs of Zika, he described a second episode of symptoms compatible with ZIKV infection 2 weeks after second episode: RNA loads were: copies/ml and copies/ml in the first and second semen samples, respectively, and copies/ml in the urine sample. ZIKV was isolated from his semen.

61 Sample Collection and Shipment Refrigerate biological fluids and tissues at 4 C immediately after collection; Tissue fragments should be fixed in 10% formalin (1 part of tissue + 9 of formalin) Transport 4-8 o C if transport within 3 days Freeze at -80 C if storage for weeks or months before processing and shipment to reference laboratory

62 How to Destroy Your Sample Keep samples without refrigeration Repeated freeze-thaw cycles - Destroys IgM - Kills the virus To avoid hemolysis: do not freeze unseparated blood

63 Obrigada! Thanks!