Predicting the Environmental Suitability and Identifying Climate and Sociodemographic Correlates of Guinea Worm (Dracunculus medinensis) in Chad.

A comprehensive understanding of the spatial distribution and correlates of infection are key for the planning of disease control programs and assessing the feasibility of elimination and/or eradication. In this work, we used species distribution modeling to predict the environmental suitability of the Guinea worm (Dracunculus medinensis) and identify important climatic and sociodemographic risk factors. Using Guinea worm surveillance data collected by the Chad Guinea Worm Eradication Program (CGWEP) from 2010 to 2022 in combination with remotely sensed climate and sociodemographic correlates of infection within an ensemble machine learning framework, we mapped the environmental suitability of Guinea worm infection in Chad. The same analytical framework was also used to ascertain the contribution and influence of the identified climatic risk factors. Spatial distribution maps showed predominant clustering around the southern regions and along the Chari River. We also identified areas predicted to be environmentally suitable for infection. Of note are districts near the western border with Cameroon and southeastern border with Central African Republic. Key environmental correlates of infection as identified by the model were proximity to permanent rivers and inland lakes, farmlands, land surface temperature, and precipitation. This work provides a comprehensive model of the spatial distribution of Guinea worm infections in Chad 2010-2022 and sheds light on potential environmental correlates of infection. As the CGWEP moves toward elimination, the methods and results in this study will inform surveillance activities and help optimize the allocation of intervention resources.

Monkeypox Virus Infections After 2 Preexposure Doses of JYNNEOS Vaccine - United States, May 2022-May 2024.

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.S. jurisdictions. These reported infections are estimated to have occurred in <1% of fully vaccinated persons. Compared with cases among unvaccinated persons, infections among fully vaccinated persons were more likely to occur among non-Hispanic White men aged 30-39 years, were associated with increased numbers of sexual partners, and resulted in less severe disease (p<0.001). Among infections in fully vaccinated persons with complete data, infections after vaccination were reported more commonly after receipt of heterologous (subcutaneous and intradermal) (46%) or homologous subcutaneous (32%) JYNNEOS vaccination than after homologous intradermal (22%) vaccination. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. The median interval between the second vaccine dose and illness onset was longer for cases among persons who had received 2 intradermal doses (median = 363 days; IQR = 221-444 days) compared with cases in persons who had received 2 subcutaneous doses (median = 263 days; IQR = 47-334 days) (p<0.001). The implications of this finding are not known; however, these data should increase confidence in the effectiveness of vaccine doses that were administered intradermally, the preferred method of administration during the peak of the outbreak when vaccine supply was limited. Persons recommended to receive the JYNNEOS vaccine should receive 2 doses, irrespective of the route of administration, and at this time, additional doses are not recommended for the affected population.

How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

COVID-19 Epidemiology during Delta Variant Dominance Period in 45 High-Income Countries, 2020-2021.

The SARS-CoV-2 Delta variant, first identified in October 2020, quickly became the dominant variant worldwide. We used publicly available data to explore the relationship between illness and death (peak case rates, death rates, case-fatality rates) and selected predictors (percentage vaccinated, percentage of the population >65 years, population density, testing volume, index of mitigation policies) in 45 high-income countries during the Delta wave using rank-order correlation and ordinal regression. During the Delta-dominant period, most countries reported higher peak case rates (57%) and lower peak case-fatality rates (98%). Higher vaccination coverage was protective against peak case rates (odds ratio 0.95, 95% CI 0.91-0.99) and against peak death rates (odds ratio 0.96, 95% CI 0.91-0.99). Vaccination coverage was vital to preventing infection and death from COVID-19 during the Delta wave. As new variants emerge, public health authorities should encourage the uptake of COVID-19 vaccination and boosters.

Changes in trachoma indicators in Kiribati with two rounds of azithromycin mass drug administration, measured in serial population-based surveys.

Baseline mapping in the two major population centers of Kiribati showed that trachoma was a public health problem in need of programmatic interventions. After conducting two annual rounds of antibiotic mass drug administration (MDA), Kiribati undertook trachoma impact surveys in 2019, using standardized two-stage cluster surveys in the evaluation units of Kiritimati Island and Tarawa. In Kiritimati, 516 households were visited and in Tarawa, 772 households were visited. Nearly all households had a drinking water source and access to an improved latrine. The prevalence of trachomatous trichiasis remained above the elimination threshold (0.2% in ≥15-year-olds) and was virtually unchanged from baseline. The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds decreased by approximately 40% from baseline in both evaluation units but remained above the 5% TF prevalence threshold for stopping MDA. TF prevalence at impact survey was 11.5% in Kiritimati and 17.9% in Tarawa. Infection prevalence in 1-9-year-olds by PCR was 0.96% in Kiritimati and 3.3% in Tarawa. Using a multiplex bead assay to measure antibodies to the C. trachomatis antigen Pgp3, seroprevalence in 1-9-year-olds was 30.2% in Kiritimati and 31.4% in Tarawa. The seroconversion rate, in seroconversion events/100 children/year, was 9.0 in Kiritimati and 9.2 in Tarawa. Seroprevalence and seroconversion rates were both assessed by four different assays, with strong agreement between tests. These results show that, despite decreases in indicators associated with infection at impact survey, trachoma remains a public health problem in Kiribati, and provide additional information about changes in serological indicators after MDA.

Treponemal Antibody Seroprevalence Using a Multiplex Bead Assay from Samples Collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey: Searching for Yaws in Nigeria.

Yaws is a chronic, relapsing disease of skin, bone, and cartilage caused by Treponema pallidum subsp. pertenue. Yaws was last reported in Nigeria in 1996, although neighboring countries have recently reported cases. We investigated serological evidence for yaws among children aged 0-14 years in Nigeria by measuring antibodies to the treponemal antigens rp17 and TmpA in blood specimens from a 2018 nationally representative HIV survey using a multiplex bead assay. The presence of antibodies to both antigens ("double positive") likely reflects current or recent treponemal infection. Overall, 1.9% (610/31,549) of children had anti-TmpA antibodies, 1.5% (476/31,549) had anti-rp17 antibodies, and 0.1% (39/31,549) were double positive. Among households, 0.5% (84/18,021) had a double-positive child, with a clustering of double-positive children. Although numbers are low, identification of antibodies to both TmpA and rp17 may warrant investigation, including more granular epidemiologic and clinical data, to assess the potential for continuing yaws transmission in Nigerian children.

DNA topoisomerase Top3ß is impacted by early life stress in the developing female and male rat brain.

DNA topoisomerases are essential for preserving genomic integrity. DNA topoisomerases induce breakage of DNA to facilitate replication and transcription by relaxing DNA and relieving supercoiling. Aberrant expression and deletions of topoisomerases are associated with psychiatric disorders such as schizophrenia and autism. Our study investigated the effects of early life stress (ELS) on three topoisomerases, Top1, Top3α, and Top3ß in the developing rat brain. Newborn rats were exposed to a predator odor stress on postnatal days 1, 2, and 3; brain tissue was collected either 30 min after the last stressor on postnatal day 3 or during the juvenile period. We found that exposure to predator odor resulted in a decrease in Top3ß expression levels in the neonatal male amygdala and in the juvenile prefrontal cortex of males and females. These data suggest that developing males and females respond differently to predator odor-induced stress. As ELS results in lower Top3ß levels, these data suggest that ELS experienced during development may have consequences for genomic structural integrity and increased mental health risk.

Mpox respiratory transmission: the state of the evidence.

The relative contribution of the respiratory route to transmission of mpox (formerly known as monkeypox) is unclear. We review the evidence for respiratory transmission of monkeypox virus (MPXV), examining key works from animal models, human outbreaks and case reports, and environmental studies. Laboratory experiments have initiated MPXV infection in animals via respiratory routes. Some animal-to-animal respiratory transmission has been shown in controlled studies, and environmental sampling studies have detected airborne MPXV. Reports from real-life outbreaks demonstrate that transmission is associated with close contact, and although it is difficult to infer the route of MPXV acquisition in individual case reports, so far respiratory transmission has not been specifically implicated. Based on the available evidence, the likelihood of human-to-human MPXV respiratory transmission appears to be low; however, studies should continue to assess this possibility.

Effect of Predeparture Testing on Postarrival SARS-CoV-2-Positive Test Results Among International Travelers - CDC Traveler-Based Genomic Surveillance Program, Four U.S. Airports, March-September 2022.

Beginning December 6, 2021, all international air passengers boarding flights to the United States were required to show either a negative result from a SARS-CoV-2 viral test taken ≤1 day before departure or proof of recovery from COVID-19 within the preceding 90 days (1). As of June 12, 2022, predeparture testing was no longer mandatory but remained recommended by CDC (2,3). Various modeling studies have estimated that predeparture testing the day before or the day of air travel reduces transmission or importation of SARS-CoV-2 by 31%-76% (4-7). Postarrival SARS-CoV-2 pooled testing data from CDC's Traveler-based Genomic Surveillance program were used to compare SARS-CoV-2 test results among volunteer travelers arriving at four U.S. airports during two 12-week periods: March 20-June 11, 2022, when predeparture testing was required, and June 12-September 3, 2022, when predeparture testing was not required. In a multivariable logistic regression model, pooled nasal swab specimens collected during March 20-June 11 were 52% less likely to be positive for SARS-CoV-2 than were those collected during June 12-September 3, after adjusting for COVID-19 incidence in the flight's country of origin, sample pool size, and collection airport (adjusted odds ratio [aOR] = 0.48, 95% CI = 0.39-0.58) (p<0.001). These findings support predeparture testing as a tool for reducing travel-associated SARS-CoV-2 transmission and provide important real-world evidence that can guide decisions for future outbreaks and pandemics.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using Traveler-based Genomic Surveillance at 4 US Airports, September 2021-January 2022.

We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.

COVID-19 on the Nile: a cross-sectional investigation of COVID-19 among Nile River cruise travellers returning to the United States, February-March 2020.

BACKGROUND: Early in the pandemic, cruise travel exacerbated the global spread of SARS-CoV-2. We report epidemiologic and molecular findings from an investigation of a cluster of travellers with confirmed COVID-19 returning to the USA from Nile River cruises in Egypt. METHODS: State health departments reported data on real-time reverse transcription-polymerase chain reaction-confirmed COVID-19 cases with a history of Nile River cruise travel during February-March 2020 to the Centers for Disease Control and Prevention (CDC). Demographic and epidemiologic data were collected through routine surveillance channels. Sequences were obtained either from state health departments or from the Global Initiative on Sharing Avian Flu Data (GISAID). We conducted descriptive analyses of epidemiologic data and explored phylogenetic relationships between sequences. RESULTS: We identified 149 Nile River cruise travellers with confirmed COVID-19 who returned to 67 different US counties in 27 states: among those with complete data, 4.7% (6/128) died and 28.1% (38/135) were hospitalized. These individuals travelled on 20 different Nile River cruise voyages (12 unique vessels). Fifteen community transmission events were identified in four states, with 73.3% (11/15) of these occurring in Wisconsin (as the result of a more detailed contact investigation in that state). Phylogenetic analyses supported the hypothesis that travellers were most likely infected in Egypt, with most sequences in Nextstrain clade 20A 93% (87/94). We observed genetic clustering by Nile River cruise voyage and vessel. CONCLUSIONS: Nile River cruise travellers with COVID-19 introduced SARS-CoV-2 over a very large geographic range, facilitating transmission across the USA early in the pandemic. Travellers who participate in cruises, even on small river vessels as investigated in this study, are at increased risk of SARS-CoV-2 exposure. Therefore, history of river cruise travel should be considered in contact tracing and outbreak investigations.

Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study.

BACKGROUND: The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection. METHODS: We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination. FINDINGS: 226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18-68; IQR 32-43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36-1659; IQR 500-885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1-8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 [IQR 6-21] for patients with HIV vs median rash burden score 6 [IQR 3-14] for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status. INTERPRETATION: Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact. FUNDING: US Centers for Disease Control and Prevention, International Society of Travel Medicine.

Determining Gaps in Publicly Shared SARS-CoV-2 Genomic Surveillance Data by Analysis of Global Submissions.

Viral genomic surveillance has been a critical source of information during the COVID-19 pandemic, but publicly available data can be sparse, concentrated in wealthy countries, and often made public weeks or months after collection. We used publicly available viral genomic surveillance data submitted to GISAID and GenBank to examine sequencing coverage and lag time to submission during 2020-2021. We compared publicly submitted sequences by country with reported infection rates and population and also examined data based on country-level World Bank income status and World Health Organization region. We found that as global capacity for viral genomic surveillance increased, international disparities in sequencing capacity and timeliness persisted along economic lines. Our analysis suggests that increasing viral genomic surveillance coverage worldwide and decreasing turnaround times could improve timely availability of sequencing data to inform public health action.

Epidemiological and molecular investigations of a point-source outbreak of Dracunculus medinensis infecting humans and dogs in Chad: a cross-sectional study.

BACKGROUND: Dracunculiasis (also known as Guinea worm disease), caused by the Dracunculus medinensis nematode, is progressing towards eradication, with a reduction in cases from 3·5 million cases in the mid-1980s to only 54 human cases at the end of 2019. Most cases now occur in Chad. On April 19, 2019, a 19-year-old woman presented with D medinensis in an area within the Salamat region of Chad, where the disease had not been previously reported. We aimed to investigate the connection between this case and others detected locally and elsewhere in Chad using a combination of epidemiological and genetic approaches. METHODS: In this cross-sectional field study, we conducted household case searches and informal group interviews in the Bogam, Liwi, and Tarh villages in Chad. All community members including children were eligible for participation in the outbreak investigation. Adult female D medinensis associated with this outbreak were collected for genetic analysis (18 from humans and two from dogs). Four mitochondrial genes and 22 nuclear microsatellite markers were used to assess relatedness of worms associated with the outbreak in comparison with other worms from elsewhere in Chad. FINDINGS: Between April 12 and Sept 6, 2019, we identified 22 human cases and two canine cases of dracunculiasis associated with 15 households. Six (40%) of the 15 affected households had multiple human or canine cases within the household. Most cases of dracunculiasis in people were from three villages in Salamat (21 [95%] of 22 cases), but one case was detected nearly 400 km away in Sarh city (outside the Salamat region). All people with dracunculiasis reported a history of consuming fish and unfiltered water. Worms associated with this outbreak were genetically similar and shared the same maternal lineage. INTERPRETATION: Molecular epidemiological results suggest a point-source outbreak that originated from a single female D medinensis, rather than newly identified sustained local transmission. The failure of the surveillance system to detect the suspected canine infection in 2018 highlights the challenge of canine D medinensis detection, particularly in areas under passive surveillance. Human movement can also contribute to dracunculiasis spread over long distances. FUNDING: The Carter Center.

SARS-CoV-2 Breakthrough Infections among US Embassy Staff Members, Uganda, May-June 2021.

The SARS-CoV-2 Delta variant emerged shortly after COVID-19 vaccines became available in 2021. We describe SARS-CoV-2 breakthrough infections in a highly vaccinated, well-monitored US Embassy community in Kampala, Uganda. Defining breakthrough infection rates in highly vaccinated populations can help determine public health messaging, guidance, and policy globally.

The chromatin remodeling protein CHD-1 and the EFL-1/DPL-1 transcription factor cooperatively down regulate CDK-2 to control SAS-6 levels and centriole number.

Centrioles are submicron-scale, barrel-shaped organelles typically found in pairs, and play important roles in ciliogenesis and bipolar spindle assembly. In general, successful execution of centriole-dependent processes is highly reliant on the ability of the cell to stringently control centriole number. This in turn is mainly achieved through the precise duplication of centrioles during each S phase. Aberrations in centriole duplication disrupt spindle assembly and cilia-based signaling and have been linked to cancer, primary microcephaly and a variety of growth disorders. Studies aimed at understanding how centriole duplication is controlled have mainly focused on the post-translational regulation of two key components of this pathway: the master regulatory kinase ZYG-1/Plk4 and the scaffold component SAS-6. In contrast, how transcriptional control mechanisms might contribute to this process have not been well explored. Here we show that the chromatin remodeling protein CHD-1 contributes to the regulation of centriole duplication in the C. elegans embryo. Specifically, we find that loss of CHD-1 or inactivation of its ATPase activity can restore embryonic viability and centriole duplication to a strain expressing insufficient ZYG-1 activity. Interestingly, loss of CHD-1 is associated with increases in the levels of two ZYG-1-binding partners: SPD-2, the centriole receptor for ZYG-1 and SAS-6. Finally, we explore transcriptional regulatory networks governing centriole duplication and find that CHD-1 and a second transcription factor, EFL-1/DPL-1 cooperate to down regulate expression of CDK-2, which in turn promotes SAS-6 protein levels. Disruption of this regulatory network results in the overexpression of SAS-6 and the production of extra centrioles.

Post-Validation Survey in Two Districts of Morocco after the Elimination of Trachoma as a Public Health Problem.

Trachoma is the leading infectious cause of blindness. In 2016, Morocco was validated by WHO as having eliminated trachoma as a public health problem. We evaluated two previously endemic districts in Morocco for trachomatous inflammation-follicular (TF), trachomatous trichiasis (TT), and antibodies against Chlamydia trachomatis, the causative agent of trachoma. Community-based cross-sectional surveys in the districts of Boumalene Dades and Agdez included 4,445 participants for whom both questionnaire and serology data were available; 58% were aged 1-9 years. Participants had eyes examined for TF and blood collected for analysis of antibodies to the C. trachomatis antigen Pgp3 by both a multiplex bead assay (MBA) and lateral flow assay (LFA). Seroconversion rates (SCR) per 100 people per year were used to estimate changes in the force of infection using Bayesian serocatalytic models. In Agdez, TF prevalence in 1-9-year-olds was 0.3%, seroprevalence ranged from 9.4% to 11.4%, and SCR estimates ranged from 2.4 to 3.0. In Boumalene Dades, TF prevalence in 1-9-year-olds was 0.07%, and modeling data from the different assays indicated a decrease in transmission between 20 and 24 years ago. The TF data support an absence of active trachoma in the two districts examined. However, seroprevalence and SCR in younger people were higher in Agdez than Boumalene Dades, showing that there can be differences in serology metrics in areas with similar TF prevalence. Data will be included in multicountry analyses to better understand potential thresholds for serological surveillance in trachoma.