Audience: Clinical Laboratory Professionals
Level: Laboratory Advisory
On October 17, 2025, the California Department of Public Health announced that it had identified three unrelated cases of clade Ib monkeypox virus (MPXV) in Southern California. Viral genomic data suggest the three September cases are likely part of the same epidemiologic cluster and may be linked to a United States clade Ib case from August 2025 with travel to an area with clade Ib MPXV spread. There is high suspicion of community transmission of clade Ib MPXV in the United States since the three cases have no history of travel and no obvious common exposure or epidemiologic link between them. Investigations and increased surveillance are ongoing, but no additional cases have been identified at this time.
The CDC continues to assess the https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dcf&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=J5S86djvUPzIfUktYU4Cxsaked0ORhBh55XAVmhLjzs. Click or tap if you trust this link." target="_blank" rel="noopener">risk of clade I MPXV to the U.S. general population as low. During recent clade Ib (a type of clade I) outbreaks in Africa, less than 0.5% of patients died from the disease.
State, local, and territorial public health authorities should promptly report cases to CDC-including orthopoxvirus generic (i.e., non-variola orthopoxvirus) positive and clade II negative test results from patients.
Because mutations may impact clade-specific PCR tests, laboratories should use a test that targets a viral essential gene (e.g., the CDC non-variola orthopoxvirus (NVO) test). Clade Ib MPXV cannot be detected by clade II-specific tests (for example, CDC-developed G2R-WA) or clade Ia specific tests (also called D14, CDC-developed C3L, CB, or Congo Basin). Any specimens that are negative by clade II and/or clade Ia-specific tests with a high suspicion of monkeypox should be sent for additional testing.
CDC recommends that laboratories using an orthopoxvirus or monkeypox virus (MPXV) generic test without additional clade-specific testing send all (or at least 80% if resource-restricted) orthopoxvirus or MPXV positive clinical specimens for clade-specific testing. If clade-specific testing is not available in a jurisdiction, https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd0&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=shppsHyCaZeZEAA8qHHAIf6fVvBt7kBM3Fn2z4yMeMY. Click or tap if you trust this link." target="_blank" rel="noopener">specimen submission to a capable public health laboratory or to CDC is encouraged. Your state or local health department can coordinate specimen submission to CDC.
CDC recommends performing clade-specific testing in all cases that meet any of the criteria below:
1) All severe cases (hospitalized)
2) All cases in vaccinated persons
3) Cases not associated with MSM population
4) Cases with travel to locations with known clade I MPXV cases
5) Cases in localities that have detected clade I MPXV for 3 months after detection of clade I case.
6) Locally acquired cases in localities that have not had monkeypox in the last 6 months
7) Positive result by MPXV or orthopoxvirus generic test AND negative or indeterminate result by clade II-specific test
Laboratories using CDC's NVO test that are not performing their own MPXV clade-specific testing should continue submitting the duplicate specimen from patients with positive NVO test results to CDC. Specimens should be submitted to CDC under surveillance OR for Clinical Laboratory Improvement Amendments (CLIA) testing.
NOTE: CDC's current ability to perform clade typing is limited with increased turnaround times due to the lapse in appropriations. Some non-CDC laboratories have other options for clade-specific testing (e.g., molecular testing or genetic sequencing). These laboratories should alert their state health department and CDC (poxvirus@cdc.gov.">https://m.emailupdates.cdc.gov/poxvirus@cdc.gov. Click or tap if you trust this link." target="_blank" rel="noopener">poxvirus@cdc.gov) if results indicate detection of clade I MPXV.
Additional guidance:
Refer to https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd1&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=66AZ3rTCXyucLIg0vaDV5pWcNQIipRN52L67jbizNJM. Click or tap if you trust this link." target="_blank" rel="noopener">HAN Health Update 516 for the most recent CDC clinical and travel guidance on clade I monkeypox. Clinicians should know symptoms of MPXV infection and ask patients about recent travel history and other risk factors and consider MPXV testing. Suspected and confirmed cases caused by clade I MPXV should be reported to the local, territorial, and state public health authorities as soon as possible. CDC recommends vaccination to people who are eligible for monkeypox vaccine, including those who may have a recent MPXV exposure.
Please review the additional resources below for recommendations and resources for clinicians and public health practitioners, health departments, laboratories, and for the public.
We encourage you to share this message widely with your network(s).
https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd2&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=YhW88vcMNCdrBwxXQHY6HgGLwWNy_mJmaoW6ifRvJJ4. Click or tap if you trust this link." target="_blank" rel="noopener">Opt in to receive updates from the CDC Laboratory Outreach Communication System.
Online Resources
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd3&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=3PoL3YV6jfw8QujLWc2nMMPXxzPS2VLqUh84Hf7MIdQ. Click or tap if you trust this link." target="_blank" rel="noopener">About Monkeypox | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd4&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=XTMsySr5Dn8THHnCdopb6MknkXucq1FboBenNPbhxIY. Click or tap if you trust this link." target="_blank" rel="noopener">Risk to United States from clade I monkeypox outbreak in Central and Eastern Africa | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd5&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=deHkHNml0QNBQ1MHwwiLUt5RqBnCuvU3nw8pbwH7hfU. Click or tap if you trust this link." target="_blank" rel="noopener">Prevention Strategies for Monkeypox, including Vaccinating People at Risk via Sexual Exposure, for U.S. Travelers Visiting Countries with Clade I Monkeypox Outbreaks | HAN
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd6&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=XKWEn6-xXZsauyr-KPxMmM1n0qJrA4UbExV6pf4GSSE. Click or tap if you trust this link." target="_blank" rel="noopener">Clinical Features of Monkeypox | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd7&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=zIzzmVC39mLLNPF09qcUlRdLQxX8v7EG0P42bdvlDk4. Click or tap if you trust this link." target="_blank" rel="noopener">Diagnostic Testing for Monkeypox | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd8&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=V0iyZzMrBM3rK82v_ChnvdnLvwOtjKjo1z5gBd46RpI. Click or tap if you trust this link." target="_blank" rel="noopener">Monkeypox Case Definitions | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dd9&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=LdpfeNqO-VKq8oc5900DBLQdiBX7FnISbogF1EQ-VLE. Click or tap if you trust this link." target="_blank" rel="noopener">Interim Clinical Considerations for Use of Vaccine for Monkeypox Prevention in the United States | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dda&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=E5tb9OZeIMjaV9kDKXg3BXcJetJOB_OpwiL0Z-EVM-4. Click or tap if you trust this link." target="_blank" rel="noopener">Monkeypox Monitoring and Risk Assessment for People Exposed in the Community | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0ddb&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=vDojPH_YMso3ykS_VuGq1yPnQEvpS1A6qXizi4tmv0k. Click or tap if you trust this link." target="_blank" rel="noopener">Test Order | Submitting Specimens to CDC | CDC
- https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0ddc&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=GkqeDSh4eT5lfmbSPWlLNxQBTnH86q-sN80tmVf4mI4. Click or tap if you trust this link." target="_blank" rel="noopener">After Hours/Epi-on-Call Contact Lists | CSTE
Questions?
Thank you,
The Laboratory Outreach Communication System
Laboratory Outreach Communication System (LOCS)
Office of Laboratory Systems and Response (OLSR)
Centers for Disease Control and Prevention (CDC)
LOCS@cdc.gov
https://t.emailupdates.cdc.gov/r/?id=h99d2d140,1f2bf2cd,1f2c0dde&e=QUNTVHJhY2tpbmdJRD1ETTE1MDg4OSZBQ1NUcmFja2luZ0xhYmVsPUxhYiUyMEFkdmlzb3J5JTNBJTIwMTAlMkYyOSUyRjIwMjUlMjBVcGRhdGUlMjBvbiUyMENsYWRlJTIwSWIlMjBNb25rZXlwb3glMjBWaXJ1cyUyMGluJTIwdGhlJTIwVW5pdGVkJTIwU3RhdGVz&s=ITzJx3wfuuc3Hq_KW0yCTJxMdnD37BhWUDjUYE6hOIc. Click or tap if you trust this link." target="_blank" rel="noopener">www.cdc.gov/locs/php/about/