# Presentation: 209547

## West Nile virus:  New modes of transmission

- Division of Vector-Borne Infectious Diseases
- Centers for Disease Control and Prevention
- Fort Collins, Colorado

## Epidemic WNME, United States, 2002

**Western hemisphere’s largest **_**arboviral**_** ME epidemic**
**2,741 WNME cases**
**1,267 WNF / unspecified**
**   ****263 deaths**
**     ****39 states & D.C.**
**Largest **_**WN**_**ME epidemic *****EVER***
**Spread to Pacific coast **
**New clinical syndromes**
**Acute flaccid paralysis (“West Nile polio”)**
**Five new transmission modes**

*** As of 2/5/2003**

- 4008 illnesses*

## WN virus infections associated with:

- Transplantation (TPX)
- Transfusion (TFX)
- Breastfeeding
- Transplacental transmission
- Occupational exposure

## VECTOR List-server

***VECTOR*** *List-server*

**Notes:**
Everything that I am going to be talking about today is the result of our cooperators reporting to ArboNET. ArboNET currently includes all 54 cooperators who were funded in 2001 to include West Nile virus surveillance. This includes the 48 continuous states plus six large independent cities that were separately funded – Washington D.C. New York City, Philadelphia, Houston, Chicago, and Los Angeles. ArboNET electronically receives reports of humans or animals that are tested for WNV infection (so-called denominator data) and of animals that are found to be positive for infection (so-called numerator data). For those of you that have not worked with us on reporting human cases, we still insist on receiving human reports by direct phone call to DVBID in Fort Collins.  With regards to upcoming changes in ArboNET, many cooperators wanted the capacity to manage and report surveillance data about all domestic arboviruses. We will be attempting to accommodate them in 2002.

## New modes of transmission

- Review previous flavi- and WN virus transmission in animals or humans
- Example of one transmission event
- Summary of reported cases
- Recommendations / comments
- Future surveillance recommendations

## TPX-associated WN virus infection

## Previous reports flavivirus transmission

- Except for HCV and HGV, _***NO***_ well-documented reports of flavivirus transmission via TPX
- Nov ‘94: Puerto Rico dengue outbreak – 6 yr old with probable transmission due to bone marrow TPX (Rigau et al AJTMH 2001)

## WN virus infection in organ donor and four organ recipients, August 2002

- Organ donor

- Blood components 63 donors

- Crash victim

**36 hours**

## WN virus infection in organ donor and four organ recipients, August 2002

**WNV PCR-neg**
**WNV IgM-neg**

- Organ Donor

- Blood components 63 donors

- Organ Donor

**36 hours**

**WNV PCR-pos**
**WNV culture-pos**
**WNV IgM-neg**

## WN virus infection in organ donor and four organ recipients, August 2002

**WNV PCR-neg**
**WNV IgM-neg**

- Organ Donor

- Blood components 63 donors

- Organ Donor

**36 hours**

**WNV PCR-pos**
**WNV culture-pos**
**WNV IgM-neg**

**F/U: 1 seroconverting donor;**
**Retrieved, stored plasma – WNV PCR-positive**

##  TPX-associated WN virus infection

- TPX-associated transmission confirmed
- High attack rate:
- 4/4 organ recipients ill
- 3/4 develop encephalitis
- Large viral load, immunosuppressive drugs
- Unusual clinical findings:
- Symptoms 7-17 days post-TPX
- Minimal CSF pleocytosis observed
- Organ donor’s infection from infectious blood unit

##  TPX-associated WN virus infection

- Prevention? Exclude viremic organ donors
- Limited exclusion tools:
- Donor illness? Young infected persons often asymptomatic
- Serology? Antibodies develop after viremia
- NAAT blood prior to organ procurement? Virus in kidneys, lungs, spleen, and CNS without viremia
- At a minimum:
- Report persons who develop WN viral illness within 4 weeks of receiving organ/tissue
- Assist in retrieval of other potentially infectious tissues

## TFX-associated WN virus infection

## Previous reports

- Except for HCV and HGV, _***NO***_ well-documented reports of other flavivirus transmission via TFX

## TFX-associated WN viral infectionPatients A (liver transplant) and B (post-partum)

**TFX-associated WN viral infection****Patients A (liver transplant) and B (post-partum)**

**9/2**

**9/5**

**Illness onset**

**CSF**** IgM +**

**8/20**

**PATIENT A (39 donors)**

**RBCs transfused**

**9/3**

**9/13**

**Illness ****onset**

**PATIENT B (2 donors)**

**9/18**

**CSF****IgM +**

**Platelets**
**transfused**

## TFX-associated WN viral infectionPatients A (liver transplant) and B (post-partum)

**TFX-associated WN viral infection****Patients A (liver transplant) and B (post-partum)**

**9/2**

**9/5**

**Illness onset**

**CSF**** IgM +**

**8/20**

**8/15**

**10/7**

**8/17**

**Serum ****IgM +**

**DONOR**

**PATIENT A (39 donors)**

**RBCs transfused**

**9/3**

**9/13**

**Illness ****onset**

**PATIENT B (2 donors)**

**9/18**

**CSF****IgM +**

**DONOR**

**Illness onset (fever, rash)**

**Platelets**
**transfused**

**Donation**

## TFX-associated WN viral infectionPatients A (liver transplant) and B (post-partum)

**TFX-associated WN viral infection****Patients A (liver transplant) and B (post-partum)**

**9/2**

**9/5**

**Illness onset**

**CSF**** IgM +**

**8/20**

**8/15**

**10/7**

**8/17**

**Serum ****IgM +**

**DONOR**

**PATIENT A (39 donors)**

**RBCs transfused**

**9/3**

**9/13**

**Illness ****onset**

**PATIENT B (2 donors)**

**9/18**

**CSF****IgM +**

**DONOR**

**Illness onset (fever, rash)**

**Platelets**
**transfused**

**Donation**

**Stored tubing segment – PCR-positive (Lab 1)**

**Retrieved plasma – PCR-equivocal (Lab 1)**

**Retrieved plasma – PCR-positive (Lab 2)**

## TFX-associated WN virus infection

- 60 investigations, Aug 2002 - Jan 2003
- 20 confirmed cases
- 14 infectious unit donors identified
- 21 on-going investigations
- 19 no transmission evidence
- > 2500 samples tested (NAAT & serology)
- Transmitted in RBCs, plasma, & platelets
- Virus isolated from one stored plasma unit
- 5 of 14 infectious donors _**asymptomatic**_
- 7 of 20 confirmed cases _**asymptomatic**_

## TFX-associated WN virus infection

- Reduce risk of TFX-associated transmission
- Defer unsuitable blood donors
- Report post-donation illnesses that suggest WN virus infection
- Withdraw & quarantine blood products from ill donors
- Diagnostics industry developing screening tests
- Testing strategies and deferral policies TBA
- Will need to investigate transfusion cases in 2003 to evaluate strategies and policies

## Transplacental WN virus transmission

## Transplacental flavivirus transmission

- Human: Vertical dengue transmission
- Moderate to severe neonatal dengue
- Human: Rare neonatal infections in asymptomatic newborns of YEL vaccinees & YF-infected mothers
- Human: Japanese encephalitis virus
- Late 70s/early 80s – India
- 9 cases of infected mothers
- 4 spontaneous abortions, 4 “normal,” 1 ?
- Previous SLE outbreaks – no neonatal infections reported
- Anecdotal report of WN virus in equine aborted fetuses
- No previous reports of transplacental WN virus infection in humans

## 20 year-old pregnant woman

- Aug

- Sep

- Oct

- Nov

- Fever, h/a, blurred vision, leg weakness, hyporeflexia

- Leaves
- AMA

## 20 year-old pregnant woman

- Aug

- Sep

- Oct

- Nov

- Fever (39.3C)
- H/A
- Blurred vision
- Leg weakness
- Hyporeflexia

- Leaves
- AMA

- Re-admit;
- fall due to
- weakness

- TORCH- & HIV-negative
- Flavivirus IgM/IgG (IFA)

## 20 year-old pregnant woman

- Aug

- Sep

- Oct

- Nov

- Fever (39.3C)
- H/A
- Blurred vision
- Leg weakness
- Hyporeflexia

- Leaves
- AMA

- Re-admit;
- fall due to
- weakness

- TORCH- & HIV-negative
- Flavivirus IgM/IgG (IFA)

- CSF pleocytosis
- WNV IgM –CSF/serum
- Abnormal EMG

## 20 year old pregnant woman

- Aug

- Sep

- Oct

- Nov

- Fever (39.3C)
- H/A
- Blurred vision
- Leg weakness
- Hyporeflexia

- Leaves
- AMA

- Re-admit;
- fall due to
- weakness

- TORCH- & HIV-negative
- Flavivirus IgM/IgG (IFA)

- CSF pleocytosis
- WNV IgM –CSF/serum
- Abnormal EMG

- Delivery
- EGA: 38 weeks

## Transplacental flavivirus transmission

- Late 2nd trimester infection
- Prolonged clinical illness (viremia?) in mother
- Child:
- Chorioretinitis; bilateral white matter loss in temporal/occipital; temporal lobe cyst
- Cord & heel-stick blood – WN virus IgM-positive
- CSF – WN virus IgM-positive
- TORCH, CMV, & LCMV antibody negative
- WN, entero-, & HS viruses all PCR negative
- Placenta/umbilical cord – WN virus PCR positive or equivocal in two labs

## Transplacental flavivirus transmission

- 1st reported human transplacental transmission of WN virus
- Infection & structural CNS abnormalities – no proven causality
- Recommendations:
- Infection screening: No
- Illness testing: Yes
- Personal protection for pregnant woman: Yes
- Voluntary birth outcome registry

## Neonatal outcome among four pregnant woman with WN viral illness

|  | Infected | Not infected | Total |
| --- | --- | --- | --- |
| Yes | 1 | 0 | 1 |
| No | 0 | 3 | 3 |
| Total | 1 | 3 | 4 |

- Four more pending - 1 unborn; 3 born but illness
- and infection not yet defined

- Neonatal illness

## Web-based reporting

- Health care providers report on-line that they care for a pregnant woman with WN virus infection
- States informed when their providers report
- Provider contacted; informed of tissues needed for testing

## Breastfeeding-associated WN virus infection

## Flavivirus transmission in milk

**Animal-to-animal:**
**Powassan virus (experimentally)**
**Louping ill virus**
**West Nile virus (experimentally; hamsters)**
**Animal-to-human:**
**Tick-borne encephalitis virus (raw sheep & goat milk/cheese)**
**Primate-to-primate:**
**Kyasanur Forest disease virus (langurs)**
**Human-to-human:**
**Hepatitis C virus**

## TFX-associated WN virus infectionPatients A (liver transplant) and B (post-partum)

**TFX-associated WN virus infection****Patients A (liver transplant) and B (post-partum)**

**9/2**

**9/5**

**Illness onset**

**CSF**** IgM +**

**8/20**

**8/15**

**10/7**

**8/17**

**Serum ****IgM +**

**DONOR**

**PATIENT A (39 donors)**

**RBCs transfused**

**9/3**

**9/13**

**Illness ****onset**

**PATIENT B (2 donors)**

**9/18**

**CSF****IgM +**

**DONOR**

**Illness onset (fever, rash)**

**Platelets**
**transfused**

**Donation**

## WN virus transmission in human milkPatients B (post-partum) and her child

**WN virus transmission in human milk****Patients B (post-partum) and her child**

**RBCs transfused**

**9/3**

**9/13**

**Illness ****onset**

**PATIENT B (2 donors)**

**9/18**

**CSF****IgM +**

**Delivery 9/2**

**Breastfed child**

**Heel-stick (baby):**
**WNV IgM-negative**

**Breast milk (mother):**
**WNV PCR & IgM positive**

**9/18**

**Breast milk (mother):**
**PCR-negative**
**IgM-positive**

**9/27**

**Serum (baby):**
**PCR-negative**
**IgM-positive**

**No evidence**
**of illness in baby**

## Flavivirus transmission in milk

- 1 of 2 youngest WN virus-infected persons ever; no illness
- No evidence for transplacental infection
- Mother not infected at delivery
- WNME 9 days after WN virus-infected unit
- Child breast-fed for first 17 days
- Low titer IgM Ab in human milk
- Passive transfer of Ab’s inefficient
- WN virus-specific IgM in infant independent production
- WN virus genetic material present transiently in milk
- Attempts to culture WN virus failed

## Flavivirus transmission in milk

- WN viral illnesses in children aged <1 year infrequently reported
- 1999-2001, no reports
- 2002, _***SIX***_ persons < 1 year old with WN virus infection reported (excluded one transplacental infection)
- Ages: 0, 1, 3, 6, 9 & 11 mos.
- 1 asymptomatic (breast feeding-associated)
- 5 WNME cases
- 1 breastfed but mother without infection
- 4 not breast fed in month prior to illness

## Occupationally-acquired WN virus infection

## Occupationally-acquired infection

- Occupational transmission of WN and Kunjin viruses among lab workers reported prior to 1999
- Percutaneous injury
- Aerosol
- In 2001, suspect case of lab-acquired WN virus infection reported in New York

## WN viral transmission through percutaneous injury of laboratory worker A

**Dr. visit ****aaa**

**WN viral transmission through percutaneous injury of laboratory worker A**

**Illness onset (h/a, chills, sweats, lymphadenopathy)**

**D4**

**Lab worker A**

**Percutaneous injury – D0**

**D6**

**Rash onset ****a**

**D7**

- Days relative to injury

## WN viral transmission through percutaneous injury of laboratory worker A

**Dr. visit ****aaa**

**WN viral transmission through percutaneous injury of laboratory worker A**

**Illness onset (h/a, chills, sweats, lymphadenopathy)**

**D4**

**Lab worker A**

**Percutaneous injury – D0**

**Serum: WNV IgM- and PCR-negative**

**D6**

**Rash onset ****a**

**D7**

**Serum: WNV IgM-positive **
**IgM P/N 10.3**

**D17**

- Days relative to injury

**Serum: WNV IgM-positive **
**IgM P/N 10.3**
**WNV neut ab 1:160**

**D25**

## WN viral transmission through percutaneous injury of laboratory worker A

**Dr. visit ****aaa**

**WN viral transmission through percutaneous injury of laboratory worker A**

**Illness onset (h/a, chills, sweats, lymphadenopathy)**

**D4**

**Lab worker A**

**Percutaneous injury – D0**

**Serum: WNV IgM- and PCR-negative**

**D6**

**Rash onset ****a**

**D7**

**Serum: WNV IgM-positive **
**IgM P/N 10.3**

**D17**

- Days relative to injury

**Serum: WNV IgM-positive **
**IgM P/N 10.3**
**WNV neut ab 1:160**

**D25**

- Blue jay brain PCR-positive

## Occupationally-acquired infection

- In 2002, 2 reported cases of occupationally acquired infection among lab workers
- Both percutaneous injury
- Performing necropsy for WN virus surveillance
- Making reagents
- Both WN fever
- Heterologous antibody to closely-related flaviviruses did not protect from illness (ameliorate illness?)

## Occupationally-acquired infection

- Anecdotal reports of illness in bird handlers
- Many people working with samples containing live virus
- Goal of surveillance
- Estimate incidence of work-related infections
- Define specific activities that result in infection so that protective interventions can be engineered
- Study role of post-exposure treatment

## Surveillance changes

- Abbreviate ArboNET data fields
- Add core data fields, questions to determine if following occurred in specified period before illness:
- Organ transplantation
- Blood transfusion
- Birth
- Breast feeding
- Work with known infectious material
- Add field to accommodate these data in local databases
- Add field to accommodate data in ArboNET software and web-based ArboNET
- Rewrite XML file format to accept data transfer from states with other systems

## Slide 44

## Slide 45

## References

- Anonymous. Laboratory safety for arboviruses and certain other viruses of vertebrates: the Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod-Borne Viruses. Am J Trop Med Hyg 1980;291:359--81.
- Pike RM. Laboratory-associated infections: summary and analysis of 3,921 cases. Health Lab Sci 1976;13:105--14.
- Sewell DL. Laboratory-associated infections and biosafety. Clin Microbiol Rev 1995;8:389--405.