Complete Genome Sequence of O'nyong Nyong Virus Isolated from a Febrile Patient in 2017 in Uganda.

Despite causing numerous large outbreaks in the 20th century, few isolates of o'nyong nyong virus (ONNV) have been fully sequenced. Here, we report the complete genome sequence of an isolate of ONNV obtained from a febrile patient in northwest Uganda in 2017, designated ONNV UVRI0804.

Epidemiology, Ecology and Prevention of Plague in the West Nile Region of Uganda: The Value of Long-Term Field Studies.

Plague, a fleaborne rodent-associated zoonosis, is a neglected disease with most recent cases reported from east and central Africa and Madagascar. Because of its low incidence and sporadic occurrence, most of our knowledge of plague ecology, prevention, and control derives from investigations conducted in response to human cases. Long-term studies (which are uncommon) are required to generate data to support plague surveillance, prevention, and control recommendations. Here we describe a 15-year, multidisciplinary commitment to plague in the West Nile region of Uganda that led to significant advances in our understanding of where and when persons are at risk for plague infection and how to reduce morbidity and mortality. These findings provide data-driven support for several existing recommendations on plague surveillance and prevention and may be generalizable to other plague foci.

Intervention To Stop Transmission of Imported Pneumonic Plague - Uganda, 2019.

Plague, an acute zoonosis caused by Yersinia pestis, is endemic in the West Nile region of northwestern Uganda and neighboring northeastern Democratic Republic of the Congo (DRC) (1-4). The illness manifests in multiple clinical forms, including bubonic and pneumonic plague. Pneumonic plague is rare, rapidly fatal, and transmissible from person to person via respiratory droplets. On March 4, 2019, a patient with suspected pneumonic plague was hospitalized in West Nile, Uganda, 4 days after caring for her sister, who had come to Uganda from DRC and died shortly thereafter, and 2 days after area officials received a message from a clinic in DRC warning of possible plague. The West Nile-based Uganda Virus Research Institute (UVRI) plague program, together with local health officials, commenced a multipronged response to suspected person-to-person transmission of pneumonic plague, including contact tracing, prophylaxis, and education. Plague was laboratory-confirmed, and no additional transmission occurred in Uganda. This event transpired in the context of heightened awareness of cross-border disease spread caused by ongoing Ebola virus disease transmission in DRC, approximately 400 km to the south. Building expertise in areas of plague endemicity can provide the rapid detection and effective response needed to mitigate epidemic spread and minimize mortality. Cross-border agreements can improve ability to respond effectively.

An Evaluation of the Flea Index as a Predictor of Plague Epizootics in the West Nile Region of Uganda.

Plague is a low incidence flea-borne zoonosis that is often fatal if treatment is delayed or inadequate. Outbreaks occur sporadically and human cases are often preceded by epizootics among rodents. Early recognition of epizootics coupled with appropriate prevention measures should reduce plague morbidity and mortality. For nearly a century, the flea index (a measure of fleas per host) has been used as a measure of risk for epizootic spread and human plague case occurrence, yet the practicality and effectiveness of its use in surveillance programs has not been evaluated rigorously. We sought to determine whether long-term monitoring of the Xenopsylla flea index on hut-dwelling rats in sentinel villages in the plague-endemic West Nile region of Uganda accurately predicted plague occurrence in the surrounding parish. Based on observations spanning ~6 yr, we showed that on average, the Xenopsylla flea index increased prior to the start of the annual plague season and tended to be higher in years when plague activity was reported in humans or rodents compared with years when it was not. However, this labor-intensive effort had limited spatial coverage and was a poor predictor of plague activity within sentinel parishes.

Rat Fall Surveillance Coupled with Vector Control and Community Education as a Plague Prevention Strategy in the West Nile Region, Uganda.

Plague, primarily a disease of rodents, is most frequently transmitted by fleas and causes potentially fatal infections in humans. In Uganda, plague is endemic to the West Nile region. Primary prevention for plague includes control of rodent hosts or flea vectors, but targeting these efforts is difficult given the sporadic nature of plague epizootics in the region and limited resource availability. Here, we present a community-based strategy to detect and report rodent deaths (rat fall), an early sign of epizootics. Laboratory testing of rodent carcasses is used to trigger primary and secondary prevention measures: indoor residual spraying (IRS) and community-based plague education, respectively. During the first 3 years of the program, individuals from 142 villages reported 580 small mammal deaths; 24 of these tested presumptive positive for Yersinia pestis by fluorescence microscopy. In response, for each of the 17 affected communities, village-wide IRS was conducted to control rodent-associated fleas within homes, and community sensitization was conducted to raise awareness of plague signs and prevention strategies. No additional presumptive Y. pestis-positive carcasses were detected in these villages within the 2-month expected duration of residual activity for the insecticide used in IRS. Despite comparatively high historic case counts, no human plague cases were reported from villages participating in the surveillance program; five cases were reported from elsewhere in the districts. We evaluate community participation and timeliness of response, report the frequency of human plague cases in participating and surrounding villages, and evaluate whether a program such as this could provide a sustainable model for plague prevention in endemic areas.

Patterns of Human Plague in Uganda, 2008-2016.

Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague. Reports of an unusual number of dead rats in a patient's village around the time of illness onset was significantly associated with laboratory confirmation of plague. This descriptive summary of human plague in Uganda highlights the episodic nature of the disease, as well as the potential that, even in endemic areas, illnesses of other etiologies might be being mistaken for plague.

Successful Treatment of Human Plague with Oral Ciprofloxacin.

The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.

Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda.

BACKGROUND: Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease. METHODOLOGY/PRINCIPAL FINDINGS: During January 2004-December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution. CONCLUSIONS/SIGNIFICANCE: We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk.

Climate predictors of the spatial distribution of human plague cases in the West Nile region of Uganda.

East Africa has been identified as a region where vector-borne and zoonotic diseases are most likely to emerge or re-emerge and where morbidity and mortality from these diseases is significant. Understanding when and where humans are most likely to be exposed to vector-borne and zoonotic disease agents in this region can aid in targeting limited prevention and control resources. Often, spatial and temporal distributions of vectors and vector-borne disease agents are predictable based on climatic variables. However, because of coarse meteorological observation networks, appropriately scaled and accurate climate data are often lacking for Africa. Here, we use a recently developed 10-year gridded meteorological dataset from the Advanced Weather Research and Forecasting Model to identify climatic variables predictive of the spatial distribution of human plague cases in the West Nile region of Uganda. Our logistic regression model revealed that within high elevation sites (above 1,300 m), plague risk was positively associated with rainfall during the months of February, October, and November and negatively associated with rainfall during the month of June. These findings suggest that areas that receive increased but not continuous rainfall provide ecologically conducive conditions for Yersinia pestis transmission in this region. This study serves as a foundation for similar modeling efforts of other vector-borne and zoonotic disease in regions with sparse observational meteorologic networks.

Evaluation of rodent bait containing imidacloprid for the control of fleas on commensal rodents in a plague-endemic region of northwest Uganda.

In recent decades, the majority of human plague cases (caused by Yersinia pestis) have been reported from Africa. In an effort to reduce the risk of the disease in this area, we evaluated the efficacy of a host-targeted rodent bait containing the insecticide imidacloprid for controlling fleas on house-dwelling commensal rodents in a plague-endemic region of northwestern Uganda. Results demonstrated that the use of a palatable, rodent-targeted, wax-based bait cube was effective at reducing the prevalence of fleas on commensal rodents and flea burdens on these animals at day 7 postbait exposure, but lacked significant residual activity, allowing flea populations to rebound in the absence of additional bait applications. Our results indicate the use of a palatable host-targeted bait block containing imidacloprid was an effective technique for quickly reducing flea numbers on rodents in northwest Uganda and, thus, could be useful for lowering the potential risk of human flea bite exposures during plague outbreaks if applied continuously during the period of risk.