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CDC ENTOMOLOGY BRANCH ACTIVITIES 12 February 2007

CDC ENTOMOLOGY BRANCH ACTIVITIES 12 February 2007. Department of Health and Human Services (HHS). US Public Health Service (USPHS) National Institutes of Health (NIH) Centers for Disease Control and Prevention (CDC) National Center for Zoonotic, Vector-borne &

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CDC ENTOMOLOGY BRANCH ACTIVITIES 12 February 2007

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  1. CDCENTOMOLOGY BRANCHACTIVITIES 12 February 2007

  2. Department of Health and Human Services (HHS) US Public Health Service (USPHS) National Institutes of Health (NIH) Centers for Disease Control and Prevention (CDC) National Center for Zoonotic, Vector-borne & Enteric Diseases (NCZVED) – Formally NCID

  3. Malaria Chagas disease Lymphatic filariasis Onchocerciasis Leishmaniasis West Nile virus Trachoma Ectoparasites Outbreak investigations Intervention: ITN, IRS, drugs Insecticide resistance Molecular & vector biology Surveillance & training OCONUS: 15 PMI countries, Guatemala, Indonesia and DoD labs ENTOMOLOGY BRANCHDiseases Activities

  4. World’s Most Dangerous Animals

  5. Vector-Borne Diseases Impact DALYS = disability adjusted life years; Data from the WHO

  6. Entomology Branch Personnel 16 FTEs + ~30 fellows, students, visiting scientists, military entomologists & others 8 FTE Entomologists: Lived overseas >50 years; field and laboratory TDY >15 yrs in more than 80 countries 2 FTE Chemists: Analytical and biological analysis of drugs and insecticides

  7. Insectaries & Malaria Research and Reference Reagent Resource (MR4) Center Insectaries - Total ~280 sq m (~2,500 sq ft) • 12 separate rooms (two for infected vectors) • Biosphere building ~90 sq m (~1,000 sq ft) • Produce >3.5 million mosquitoes/year, to include all primary vectors of human malaria MR4 Vector Reagents • Living Anopheles stocks (~50 species/strains) • Field specimens/genomic-DNA; LN2 ~80,000

  8. WHO Collaborating Centers • Malaria Vector Identification - ELISA • Insecticide Resistance in Vectors • Evaluation of Existing and New Insecticides • Evaluation of Anti-malarial Drugs (pending) • Malaria Control (MB) • Control/Elimination LF in the Americas (PDB) • Human African Trypanosomiasis (PDB)

  9. Malaria: Worldwide ~500 million new infections annually; >1.4 million/day >1 million deaths/yr; a child dies every 20-30 sec A disease of the poor, ~60% in poorest ~20% Increasing problem in cities, now with ~15% of burden 1-4% loss in African GDP; ~US$12B/yr Over 40% worlds’ population is at risk ~10,000 travelers from Europe, Japan and NA (~2,000) contract malaria each year No vaccine; effective drugs expensive/counterfeited Resistant: parasites to drugs & vectors to insecticides

  10. Malaria models for evaluation of drugs, vaccines and vector competency Dr. Collins – 53 years at CDC; “…a national treasure…”

  11. Identification of Malaria Vectors • Only ~40 of ~430 Anopheles species are important vectors of human malarias • Vector collection and ID a challenge

  12. Need Replacement for HLC Human landing collections

  13. Primary Malaria Vector Complexes

  14. Vector Competency/Parasite Interactions

  15. ELISA: >2M VecTest: >45K

  16. Molecular Lab: pop’n genetics & transgenics Germ line transformation of An. gambiae with GFP-transposable element

  17. Insecticide Resistance Surveillance Program • LARVAL & ADULT BIOASSAYS • BIOCHEMICAL ASSAYS • MOLECULAR ASSAYS • MOSQUITO POOLS • FIELD STUDIES AND TRAINING

  18. ADULT RESISTANCE BOTTLE BIOASSAY Bottle treated with insecticide only Susceptible population Test population

  19. MICRO-PLATE BIOCHEMICAL ASSAYS

  20. MOLECULAR ASSAYS: Measure insecticide resistance genes……. Copy Number Expression Level Point Mutations

  21. EB Chemistry Activity • Anti-malarial drug analysis • Resistance vs. compliance • Pharmacokinetics • QA of pharmaceuticals • Counterfeit drug detection • Insecticide/formulation testing • ITN efficacy evaluations • New ITN treatment methods

  22. Analytical Testing Capability for all Available Anti-Malarial Drugs Biguanides and Biguanide/ Quinoline compounds: sulfa combinations: Quinine/ Quinidine Chloroquine Proguanil Amodiaquine Proguanil/ sulfone Mefloquine Halofantrine Miscellaneous: Primaquine Tetracyclines Clindamycin Antifol combinations: Atovaquone (+ Proguanil) Pyrimethamine/ sulfadoxine Pyronaridine Pyrimethamine/ sulfalene Azithromycin Trimethoprim/ sulfamethoxazole Artemisinins Benflumetol (+ Artemether)

  23. Malaria Therapy Drug Costs Chloroquine or SP US$ 0.10 Mefloquine US$ 3.00 Artemisinins US$ 3.70 Malarone US$ 8.00

  24. Assay: <10 minutes; >99% of tablet available for use2001-4: No artesunate in 38% OTC tablets in Vietnam, Laos, and Myanmar; ~50% OTC Cambodia counterfeitAfrica with expensive combination therapy = ?

  25. GC Analysis ITN Bioassay

  26. Laboratory Evaluation of LLTNs

  27. DPD Domestic Malaria Activities • Prevention & Treatments Guidelines • Drug options, other prevention options • Malaria case management in the United States • Prevention Communication • “Health Information for International Travel” • Building and updating interactive WEB pages • Assist states: lab support & outbreak investigations

  28. CDC Assists States in Malaria Outbreaks:63 in 59 years (1957-2006) 1 2 3 4 5 6 17 Routes of Migration

  29. Laboratory Diagnosis of Malaria PCR based Diagnosis Microscopic Based Diagnosis rRNA Genes Giemsa Stained Morphology

  30. Molecular Analysis of PBC P. vivax PBC_MSP3B(S) • MSP-3a/-b & CSP VK210 genes identical by sequence or RFLP. • S-type rRNA and ORF 470 genes of New World type • Conclusion: All 8 P. vivax infections likely originated from a single source of infection from Latin America PBC_MSP3B(F) PBC_MSP3B(MOC) Ao.1 67B.1 67T.5 56 IEC.2 Belem IEC.8 VA_KM3B VA_JB3B VA_NF3B Cey57 SL.3 India 69.1 Bangl NK Thai 781T SalI Chess BellT 781B MSP-3b Phenogram

  31. CDC OCONUS Malaria Activities LSTM GF PMI: ANG, BEN, TAZ, UGA, SEN, MOZ, GAH, MALI, LIB, ETH, RWA KEN, ZAM, MAD, MLWI PMI India CDC/KEMRI Indonesia CDC TZ Amazon Malaria Initiative CDC person in country PMI supported programs CDC Regional projects Single country support programs

  32. Amazon Malaria Initiative (AMI) CDC assists with surveillance, treatment, drug resistance, vector control & training Countries: Bolivia, Brazil, Colombia, Ecuador, Peru, Guyana, Suriname, Venezuela Partners: USAID, PAHO, NMRCD, CDC and MOHs

  33. CDC Entomology Support in Indonesia High Medium Low None CDC entomological support = Level of malaria transmission

  34. CDC Malaria Activities: Indonesia • ~2 million cases & 40,000 deaths annually • Range of transmission intensities & ecologies • Support from partners, e.g., USAID, UNICEF, GF • Opportunities to learn how to drive transmission to ever lower levels — relevance to Africa • Post-tsunami entomological evaluation & now have a Ent Br FTE entomologist in Indonesia

  35. President’s Malaria Initiative (PMI) A 5-year, $1.2 B initiative to rapidly scale-up malaria control interventions in high burden countries in Africa. Goal: Reduce malaria-related mortality by 50% in 15 countries

  36. PMI Malaria Control Tools • Transmission reduction – insecticide treated nets (ITNs), indoor residual spraying (IRS) & larval control • Case management using rapid diagnostic tests (RDT) & artemisinin combination treatment (ACT) • Intermittent Preventive Treatment in pregnancy (IPTp) • CDC has made important contributions to developing, evaluating and improving these strategies

  37. CDC/KEMRI laboratoryy at Kisian Gem Equator Provincial Hospital Kisumu Asembo Lake Victoria KENYA CDC/KEMRI Field Station Western Kenya

  38. KENYA ITN SUMMARY: 120,000 people 38%  Parasitemia 47%  Severe anemia 35%  Placental malaria 28%  Low birth weight ITNs Mosquitoes Healthier pregnancies 95% fewer An gambiae 90% reduction in transmission Healthier children 74%  Malaria attack rate Median time to 1st infection 4.5 10.7 mo 60%  Incidence of severe anemia Improved infant and child growth 27%  Sick child visits to the clinic Improved infant and child survival 26%  Infant mortality 14%  Child (1-4yr) mortality

  39. Field Evaluation of LLTNs – Essential for PMI PermaNet Cyclodextrin DAWA Olyset Conventional Insector *Failure defined as 2 consecutive bioassays with <50% mortality

  40. Indoor Residual Spraying Entire household protected No change in human behavior required • Coordinate IRS with MOH & contractor • Evaluate insecticides & formulations • Evaluate more efficient application methods, e.g. ULV Photo courtesy of Dr Mark Benedict

  41. Experimental Hut DDT Studies Ifakara - March 07 • Brazil = An. darlingi • Monitor entering, exiting & biting. • Sprayed vs. unsprayed houses • Spatial Repellent action stopped >95% from entering house • Behavioral actions> 12 months • Tanzania = An. gambiae

  42. Insecticide Based Control • Other materials- eave curtains, calendars/posters • Excito-repellents & MOA studies • Goal: Efficacy of IRS & distribution ease of ITNs

  43. Chagas Disease Cases: 16-18 million Deaths: 50,000 /yr At risk: 90 million; 21 countries Control: Three multi-national control programs (Southern Cone, Andean Pact, and CA) Agent: Trypanosoma cruzi Vector:Triatomine bugs Transmission: Vector-borne >80% Transfusion ~16% No effective treatment for established infections New drugs needed

  44. Chagas Disease Insecticide-Based Vector Control Obstacles • Incomplete domestic coverage • Reinfestation by peridomestic/ sylvatic populations (T. dimidiata in CA; T. sordida and T. brasiliensis in SA) • Insufficient post-treatment surveillance • Effects on non-target insects • Cost and long term sustainability

  45. Molecular Approach: Bacterial symbiont Rhodococcus rhodnii and Chagas parasite Trypanosoma cruzi live in the gut of Rhodnius prolixus bugs

  46. Symbionts transmitted to nymphs by coprophagy - the ingestion of feces Insects not acquiring the symbionts die

  47. (Transmission) (No Transmission) Reinfect insect Cure Insect with transformed of symbiont symbiont Isolate Transform symbiont symbiont Genetically Modified (GM) Bacterial Symbionts

  48. Ongoing Studies • Acute toxicity in normal and T-cell deficient mice (completed) • Chronic toxicity/ allergenicity studies (ongoing) • Lab/Greenhouse efficacy studies (ongoing) • GGC Proposal

  49. Lymphatic Filariasis (LF) >120 million infected in over 80 countries Over 1 billion people at risk Second leading cause of disability worldwide High disease burdens: India, Nigeria, Indonesia Mosquito-borne, including vectors of malaria Elimination is a public health goal No vaccine; mass drug administration, hygiene and mosquito control

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