Surveillance of Complicated Mpox Cases Unresponsive to Oral Tecovirimat in Los Angeles County, 2022.

The Los Angeles County Department of Public Health established a surveillance system to identify complicated (advanced human immunodeficiency virus [HIV] or hospitalized) mpox cases. From 1 August to 30 November 2022, we identified 1581 mpox cases, of which 134 (8.5%) were complicated. A subset of 8 cases did not recover after either initiating or completing a course of oral tecovirimat. All 8 patients were HIV positive and had advanced HIV (CD4 count <200 cells/µL). We identified 8 distinct mutations previously associated with tecovirimat resistance in specimens collected from 6 patients. Ongoing surveillance of viral evolution requires close coordination between health departments and frontline providers.

Mpox Outbreak - Los Angeles County, California, May 4-August 17, 2023.

Since May 2022, approximately 2,500 mpox cases have been reported in Los Angeles County (LAC), California. Beginning in May 2023, the LAC Department of Public Health observed a consistent increase in mpox cases after a prolonged period of low incidence. A total of 56 cases were identified during May 4-August 17, 2023. A minority of mpox patients were fully vaccinated (29%). One patient was hospitalized; no deaths were reported. Two cases of reinfection occurred, both of which were associated with mild illness. The increasing number of cases during this period was significant, as few other health departments in the United States reported an increase in mpox cases during the same period. The outbreak spread similarly to the 2022 U.S. mpox outbreak, mainly through sexual contact among gay, bisexual, and other men who have sex with men. Vaccination against mpox became available in June 2022 and has been shown to be effective at preventing mpox disease. This outbreak was substantially smaller than the 2022 mpox outbreak in LAC (2,280 cases); possible explanations for the lower case count include increased immunity provided from vaccination against mpox and population immunity from previous infections. Nonetheless, mpox continues to spread within LAC, and preventive measures, such as receipt of JYNNEOS vaccination, are recommended for persons at risk of Monkeypox virus exposure.

Epidemiologic Characteristics of Mpox among People Experiencing Homelessness, Los Angeles County, California, USA, 2022.

In Los Angeles County, California, USA, public health surveillance identified 118 mpox cases among persons experiencing homelessness (PEH) during July-September 2022. Age and sex were similar for mpox case-patients among PEH and in the general population. Seventy-one (60%) PEH mpox case-patients were living with HIV, 35 (49%) of them virally suppressed. Hospitalization was required for 21% of case-patients because of severe disease. Sexual contact was likely the primary mode of transmission; 84% of patients reported sexual contact <3 weeks before symptom onset. PEH case-patients lived in shelters, encampments, cars, or on the street, or stayed briefly with friends or family (couch surfed). Some case-patients stayed at multiple locations during the 3-week incubation period. Public health follow-up and contact tracing detected no secondary mpox cases among PEH in congregate shelters or encampments. Equitable efforts should continue to identify, treat, and prevent mpox among PEH, who often experience severe disease.

Excess Mortality Associated With the COVID-19 Pandemic-Los Angeles County, March-September 2020.

OBJECTIVE: To more comprehensively estimate COVID-19-related mortality in Los Angeles County by determining excess all-cause mortality and pneumonia, influenza, or COVID (PIC) mortality. DESIGN: We reviewed vital statistics data to identify deaths registered in Los Angeles County between March 15, 2020, and August 15, 2020. Deaths with an ICD-10 (International Classification of Diseases, Tenth Revision) code for pneumonia, influenza, or COVID-19 listed as an immediate or underlying cause of death were classified as PIC deaths. Expected deaths were calculated using negative binomial regression. Excess mortality was determined by subtracting the expected from the observed number of weekly deaths. The Department of Public Health conducts surveillance for COVID-19-associated deaths: persons who died of nontraumatic/nonaccidental causes within 60 days of a positive COVID-19 test result were classified as confirmed COVID-19 deaths. Deaths without a reported positive SARS-Cov-2 polymerase chain reaction result were classified as probable COVID-19 deaths if COVID-19 was listed on their death certificate or the death occurred 60 to 90 days of a positive test. We compared excess PIC deaths with the number of confirmed and probable COVID-19 deaths ascertained by surveillance. SETTING: Los Angeles County. PARTICIPANTS: Residents of Los Angeles County who died. MAIN OUTCOME MEASURE: Excess mortality. RESULTS: There were 7208 excess all-cause and 5128 excess PIC deaths during the study period. The Department of Public Health also reported 5160 confirmed and 323 probable COVID-19-associated deaths. CONCLUSIONS: The number of excess PIC deaths estimated by our model was approximately equal to the number of confirmed and probable COVID-19 deaths identified by surveillance. This suggests our surveillance definition for confirmed and probable COVID-19 deaths might be sufficiently sensitive for capturing the true burden of deaths caused directly or indirectly by COVID-19.

The Relationship Between the Human Immunodeficiency Virus-1 Transmission Network and the HIV Care Continuum in Los Angeles County.

BACKGROUND: Public health action combating human immunodeficiency virus (HIV) includes facilitating navigation through the HIV continuum of care: timely diagnosis followed by linkage to care and initiation of antiretroviral therapy to suppress viral replication. Molecular epidemiology can identify rapidly growing HIV genetic transmission clusters. How progression through the care continuum relates to transmission clusters has not been previously characterized. METHODS: We performed a retrospective study on HIV surveillance data from 5226 adult cases in Los Angeles County diagnosed from 2010 through 2014. Genetic transmission clusters were constructed using HIV-TRACE. Cox proportional hazard models were used to estimate the impact of transmission cluster growth on the time intervals between care continuum events. Gamma frailty models incorporated the effect of heterogeneity associated with genetic transmission clusters. RESULTS: In contrast to our expectations, there were no differences in time to the care continuum events among individuals in clusters with different growth dynamics. However, upon achieving viral suppression, individuals in high growth clusters were slower to experience viral rebound (hazard ratio 0.83, P = .011) compared with individuals in low growth clusters. Heterogeneity associated with cluster membership in the timing to each event in the care continuum was highly significant (P < .001), with and without adjustment for transmission risk and demographics. CONCLUSIONS: Individuals within the same transmission cluster have more similar trajectories through the HIV care continuum than those across transmission clusters. These findings suggest molecular epidemiology can assist public health officials in identifying clusters of individuals who may benefit from assistance in navigating the HIV care continuum.

Effectiveness of JYNNEOS vaccine against symptomatic mpox disease in adult men in Los Angeles County, August 29, 2022 to January 1, 2023.

We describe real-world estimates of JYNNEOS vaccine effectiveness (VE) against symptomatic mpox in Los Angeles County (LAC). We conducted a retrospective cohort study of men aged ≥18 years residing in LAC who were at risk for mpox and eligible for the JYNNEOS vaccine from 5/19/2022 to 1/1/2023. Case demographics and route of JYNNEOS administration were obtained through vaccine administration data systems. HIV and sexually transmitted infection (STI) status was obtained through disease reporting systems for HIV and STI diagnoses in LAC. To estimate VE, we calculated weekly incidence of confirmed mpox for unvaccinated, partially vaccinated (episode date ≥14 days after first dose), and fully vaccinated (episode date ≥14 days after second dose) cohorts starting on 8/29/2022, when fully vaccinated coverage exceeded 3 %, and ending on 1/1/2023. Overall, 2,171 men had confirmed mpox, and 1,002 (46 %) of those were persons living with diagnosed HIV (PLWDH). 2,019 (93 %) mpox cases were unvaccinated, 114 (5 %) were partially vaccinated and 38 (2 %) were fully vaccinated. VE was 69 % (95 % CI 59-77) for partially vaccinated and 84 % (95 % CI 80-87) for fully vaccinated individuals. Among PLWDH, VE was 72 % (95 % CI 57-82) for fully vaccinated and 28 % (95 % CI -96 to 73) VE for partially vaccinated individuals. Among persons not living with diagnosed HIV, VE was 88 % (95 % CI 86-90) for fully vaccinated and 80 % (95 % CI 76-83) for partially vaccinated individuals. Of 111 individuals hospitalized with mpox, one was partially vaccinated, and the remaining were unvaccinated. Our results align with other published studies that reported that two doses of the JYNNEOS vaccine provided significant protection against symptomatic mpox.

Interplay Between Geography and HIV Transmission Clusters in Los Angeles County.

BACKGROUND: Clusters of HIV diagnoses in time and space and clusters of genetically linked cases can both serve as alerts for directing prevention and treatment activities. We assessed the interplay between geography and transmission across the Los Angeles County (LAC) HIV genetic transmission network. METHODS: Deidentified surveillance data reported for 8186 people with HIV residing in LAC from 2010 through 2016 were used to construct a transmission network using HIV-TRACE. We explored geographic assortativity, the tendency for people to link within the same geographic region; concordant time-space pairs, the proportion of genetically linked pairs from the same geographic region and diagnosis year; and Jaccard coefficient, the overlap between geographical and genetic clusters. RESULTS: Geography was assortative in the genetic transmission network but less so than either race/ethnicity or transmission risk. Only 18% of individuals were diagnosed in the same year and location as a genetically linked partner. Jaccard analysis revealed that cis-men and younger age at diagnosis had more overlap between genetic clusters and geography; the inverse association was observed for trans-women and Blacks/African Americans. CONCLUSIONS: Within an urban setting with endemic HIV, genetic clustering may serve as a better indicator than time-space clustering to understand HIV transmission patterns and guide public health action.

Sorting by Race/Ethnicity Across HIV Genetic Transmission Networks in Three Major Metropolitan Areas in the United States.

An important component underlying the disparity in HIV risk between race/ethnic groups is the preferential transmission between individuals in the same group. We sought to quantify transmission between different race/ethnicity groups and measure racial assortativity in HIV transmission networks in major metropolitan areas in the United States. We reconstructed HIV molecular transmission networks from viral sequences collected as part of HIV surveillance in New York City, Los Angeles County, and Cook County, Illinois. We calculated assortativity (the tendency for individuals to link to others with similar characteristics) across the network for three candidate characteristics: transmission risk, age at diagnosis, and race/ethnicity. We then compared assortativity between race/ethnicity groups. Finally, for each race/ethnicity pair, we performed network permutations to test whether the number of links observed differed from that expected if individuals were sorting at random. Transmission networks in all three jurisdictions were more assortative by race/ethnicity than by transmission risk or age at diagnosis. Despite the different race/ethnicity proportions in each metropolitan area and lower proportions of clustering among African Americans than other race/ethnicities, African Americans were the group most likely to have transmission partners of the same race/ethnicity. This high level of assortativity should be considered in the design of HIV intervention and prevention strategies.

HIV transmission networks among transgender women in Los Angeles County, CA, USA: a phylogenetic analysis of surveillance data.

BACKGROUND: Transgender women are among the groups at highest risk for HIV infection, with a prevalence of 27·7% in the USA; and despite this known high risk, undiagnosed infection is common in this population. We set out to identify transgender women and their partners in a molecular transmission network to prioritise public health activities. METHODS: Since 2006, HIV protease and reverse transcriptase gene (pol) sequences from drug resistance testing have been reported to the Los Angeles County Department of Public Health and linked to demographic data, gender, and HIV transmission risk factor data for each case in the enhanced HIV/AIDS Reporting System. We reconstructed a molecular transmission network by use of HIV-TRAnsmission Cluster Engine (with a pairwise genetic distance threshold of 0·015 substitutions per site) from the earliest pol sequences from 22 398 unique individuals, including 412 (2%) self-identified transgender women. We examined the possible predictors of clustering with multivariate logistic regression. We characterised the genetically linked partners of transgender women and calculated assortativity (the tendency for people to link to other people with the same attributes) for each transmission risk group. FINDINGS: 8133 (36·3%) of 22 398 individuals clustered in the network across 1722 molecular transmission clusters. Transgender women who indicated a sexual risk factor clustered at the highest frequency in the network, with 147 (43%) of 345 being linked to at least one other person (adjusted odds ratio [aOR] 2·0, p=0·0002). Transgender women were assortative in the network (assortativity 0·06, p<0·001), indicating that they tended to link to other transgender women. Transgender women were more likely than expected to link to other transgender women (OR 4·65, p<0·001) and cisgender men who did not identify as men who have sex with men (MSM; OR 1·53, p<0·001). Transgender women were less likely than expected to link to MSM (OR 0·75, p<0·001), despite the high prevalence of HIV among MSM. Transgender women were distributed across 126 clusters, and cisgender individuals linked to one transgender woman were 9·2 times more likely to link to a second transgender woman than other individuals in the surveillance database. Reconstruction of the transmission network is limited by sample availability, but sequences were available for more than 40% of diagnoses. INTERPRETATION: Clustering of transgender women and the observed tendency for linkage with cisgender men who did not identify as MSM, shows the potential to use molecular epidemiology both to identify clusters that are likely to include undiagnosed transgender women with HIV and to improve the targeting of public health prevention and treatment services to transgender women. FUNDING: California HIV and AIDS Research Program and National Institutes of Health-National Institute of Allergy and Infectious Diseases.