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Background and Objective: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. Methods: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. Results: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1–11.4) units of blood per patient, compared with 9.1 (95% CI 9.0–9.2) units of blood per patient at the fixed-dose alternative. Conclusions: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life. [ABSTRACT FROM AUTHOR]

Background: Sickle cell anaemia is a common global life-threatening haematological disorder. Most affected births occur in sub-Saharan Africa where children usually go undiagnosed and die early in life. Uganda's national sickle cell screening programme was developed in response to a 2014 sickle cell surveillance study that documented a high disease prevalence. Objective: This study describes the temporal and financial aspects of Uganda's 2014–2019 sickle cell screening programme. Methods: National sickle cell screening data from Uganda's Central Public Health Laboratories were used to calculate turn-around times (TATs) from sample collection to delivery, testing, and result reporting for blood samples collected from February 2014 to March 2019. The parameters affecting specific TATs were assessed. The exact programme expenditures were analysed to determine cost per test and per positive sickle cell disease case detected. Results: A total of 278 651 samples were analysed. The median TAT from sample collection to laboratory receipt was 8 days (interquartile range [IQR]: 6–12), receipt to testing was 3 days (IQR: 1–7), and testing to result reporting was 6 days (IQR: 3–12). Altogether, the sample continuum averaged 16 days (IQR: 11–24). Lower level healthcare facilities were associated with longer sample delivery TATs. Calendar months (January and December) and larger sample volumes impacted testing and result reporting TATs. The cost per test was $4.46 (United States dollars [USD]) and $483.74 USD per positive case detected. Conclusion: Uganda's sickle cell screening programme is efficient and cost-effective. Universal newborn screening is the best strategy for detecting sickle cell anaemia in Uganda. [ABSTRACT FROM AUTHOR]

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Rodents pose a significant threat to human health, particularly in rural subsistence farming communities in Africa, where rodents threaten food security and serve as reservoirs of human pathogens, including the agents of plague, leptospirosis, murine typhus, rat-bite fever, Lassa fever, salmonellosis, and campylobacteriosis. Our study focused on the plague-endemic West Nile region of Uganda, where a majority of residents live in Uganda government-defined poverty, rely on subsistence farming for a living, and frequently experience incursions of rodents into their homes. In this study, we show that rodent removal was achieved in a median of 6 days of intensive lethal trapping with multiple trap types (range: 0–16 days). However, rodent abundance in 68.9% of homesteads returned to pretreatment levels within a median of 8 weeks (range 1–24 weeks), and at least a single rodent was captured in all homesteads by a median of 2 weeks (range 1–16 weeks) after removal efforts were terminated. Results were similar between homesteads that practiced rodent control whether or not their neighbors implemented similar strategies. Overall, intensive lethal trapping inside homes appears to be effective at reducing rodent abundance, but control was short lived after trapping ceased. [ABSTRACT FROM AUTHOR]

Rodents pose serious threats to human health and economics, particularly in developing countries where the animals play a dual role as pests: they are reservoirs of human pathogens, and they inflict damage levels to stored products sufficient to cause food shortages. To assess the magnitude of the damage caused by rodents to crops, their level of contact with humans, and to better understand current food storage and rodent control practices, we conducted a survey of 37 households from 17 subsistence farming villages within the West Nile region of Uganda. Our survey revealed that rodents cause both pre- and post-harvest damage to crops. Evidence of rodent access to stored foods was reported in conjunction with each of the reported storage practices. Approximately half of the respondents reported that at least one family member had been bitten by a rat within the previous three months. Approximately two-thirds of respondents practiced some form of rodent control in their homes. The abundance of rodents was similar within homes that practiced or did not practice rodent control. Together, our results show that current efforts are inadequate for effectively reducing rodent abundance in homes. [ABSTRACT FROM PUBLISHER]

Background: Sickle cell anemia (SCA) is the most common inherited hemoglobinopathy worldwide. Infection is a major cause of illness and death in children with SCA, especially in sub-Saharan Africa where an estimated 50-90% of affected children die before their fifth birthday. Interventions to reduce the incidence and severity of infections are needed urgently. A high proportion of adults and children with SCA are zinc-deficient, and zinc deficiency leads to impaired immunity and an increased risk of infection. Zinc supplementation has been shown to decrease the risk of infection in adolescents and adults, but there are no data on the effectiveness of zinc for prevention of infection in children < 5 years of age with SCA.Methods/design: The study will be a randomized, placebo-controlled, double-blind clinical trial in which 250 Ugandan children 1.00-4.99 years of age with SCA will receive daily zinc supplementation (10 mg oral dispersible tablet) or identical placebo for 12 months.Discussion: If this trial shows a reduction in severe or invasive infection incidence, it would be the basis for a multi-site, multi-country clinical trial to assess real-world safety and efficacy of zinc in African children with SCA. Since zinc is safe, inexpensive, and easy to administer, this trial has the potential to improve the health of hundreds of thousands of African children with SCA through reduction of infection-related morbidity and mortality.Trial Registration: Clinicaltrials.gov, NCT03528434. Registered on May 17, 2018 Protocol Version: 1.0. Date: Dec 11, 2017 Sponsor: Indiana University. Sponsor's protocol identifier, 1712339562. [ABSTRACT FROM AUTHOR]

Background: Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown.Methods: In a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day). The primary outcome was a hemoglobin level of 9.0 g or more per deciliter or a fetal hemoglobin level of 20% or more after 24 months. Secondary outcomes included the incidences of malaria, vaso-occlusive crises, and serious adverse events.Results: Children received hydroxyurea at a fixed dose (94 children; mean [±SD] age, 4.6±1.0 years) or with dose escalation (93 children; mean age, 4.8±0.9 years); the mean doses were 19.2±1.8 mg per kilogram per day and 29.5±3.6 mg per kilogram per day, respectively. The data and safety monitoring board halted the trial when the numbers of clinical events were significantly lower among children receiving escalated dosing than among those receiving a fixed dose. At trial closure, 86% of the children in the dose-escalation group had reached the primary-outcome thresholds, as compared with 37% of the children in the fixed-dose group (P<0.001). Children in the dose-escalation group had fewer sickle cell-related adverse events (incidence rate ratio, 0.43; 95% confidence interval [CI], 0.34 to 0.54), vaso-occlusive pain crises (incidence rate ratio, 0.43; 95% CI, 0.34 to 0.56), cases of acute chest syndrome or pneumonia (incidence rate ratio, 0.27; 95% CI, 0.11 to 0.56), transfusions (incidence rate ratio, 0.30; 95% CI, 0.20 to 0.43), and hospitalizations (incidence rate ratio, 0.21; 95% CI, 0.13 to 0.34). Laboratory-confirmed dose-limiting toxic effects were similar in the two groups, and there were no cases of severe neutropenia or thrombocytopenia.Conclusions: Among children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to that of fixed-dose hydroxyurea, with equivalent safety. (Funded by the Doris Duke Charitable Foundation and the Cincinnati Children's Research Foundation; NOHARM MTD ClinicalTrials.gov number, NCT03128515.). [ABSTRACT FROM AUTHOR]

Abstract: After starting hydroxyurea treatment, Ugandan children with sickle cell anemia had 60% fewer severe or invasive infections, including malaria, bacteremia, respiratory tract infections, and gastroenteritis, than before starting hydroxyurea treatment (incidence rate ratio, 0.40 [95% confidence interval, 0.29-0.54]; P < .001)., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: High-income countries have increased the use of simulation-based training and assessment for surgical education. Learners in low- and middle-income countries may have different educational needs and levels of autonomy but they and their patients could equally benefit from the procedural training simulation provides. We sought to characterize the current state of surgical skills simulation in East, Central, and Southern Africa and determine residents' perception and future interest in such activities., Methods: A survey was created via collaboration and revision between trainees and educators with experiences spanning high-income countries and low- and middle-income countries. The survey was administered on paper to 76 trainees (PGY2-3) who were completing the College of Surgeons of East, Central, and Southern Africa (COSECSA) Membership of the College of Surgeons examination in Kampala, Uganda in December 2019. Data from paper responses were summarized using descriptive statistics and frequencies., Results: We received responses from 43 trainees (57%) from 11 countries in sub-Saharan Africa who participated in the examination. Fifty-eight percent of respondents reported having dedicated space for surgical skills simulation training, and most (91%) had participated in some form of simulation activity at some point in their training. However, just 16% used simulation as a regular part of training. The majority of trainees (90%) felt that surgical skills learned in simulation were transferrable to the operating room and agreed it should be a required part of training. Seventy-one percent of trainees felt that simulation could objectively measure technical skills, and 73% percent of respondents agreed that simulation should be integrated into formal assessment. However, residents split on whether proficiency in simulation should be achieved prior to operative experience (54%) and if nontechnical skills could be measured (51%). The most common cited barriers to the integration of surgical simulation into residents' education were lack of suitable tools and models (85%), funding (73%), and maintenance of facilities (49%)., Conclusions: Residents from East, Central, and Southern Africa strongly agree that simulation is a valuable educational tool and ought to be required during their surgical residency. Barriers to achieving this goal include availability of affordable tools, adequate funding and confidence in the value of the educational experience. Trainees affirm further efforts are necessary to make simulation more widely available in these contexts., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

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.

Rattus rattus was first reported from the West Nile Region of Uganda in 1961, an event that preceded the appearance of the first documented human plague outbreak in 1970. We investigated how invasive R. rattus and native small mammal populations, as well as their fleas, have changed in recent decades. Over an 18-month period, a total of 2,959 small mammals were captured, sampled, and examined for fleas, resulting in the identification of 20 small mammal taxa that were hosts to 5,109 fleas (nine species). Over three-fourths (75.8%) of captured mammals belonged to four taxa: R. rattus, which predominated inside huts, and Arvicanthis niloticus, Mastomys sp., and Crocidura sp., which were more common outside huts. These mammals were hosts for 85.8% of fleas collected, including the efficient plague vectors Xenopsylla cheopis and X. brasiliensis, as well as likely enzootic vectors, Dinopsyllus lypusus and Ctenophthalmus bacopus. Flea loads on small mammals were higher in certain environments in villages with a recent history of plague compared to those that lacked such a history. The significance of these results is discussed in relation to historical data, the initial spread of plague in the WNR and the continuing threat posed by the disease., (© 2020 The Society for Vector Ecology.)

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., (Published by Oxford University Press on behalf of Entomological Society of America 2019.)

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.

Plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused by Yersinia pestis. We sought to identify risk factors for plague by comparing villages with and without a history of human plague cases within a model-defined plague focus in the West Nile Region of Uganda. Although rat (Rattus rattus) abundance was similar inside huts within case and control villages, contact rates between rats and humans (as measured by reported rat bites) and host-seeking flea loads were higher in case villages. In addition, compared with persons in control villages, persons in case villages more often reported sleeping on reed or straw mats, storing food in huts where persons sleep, owning dogs and allowing them into huts where persons sleep, storing garbage inside or near huts, and cooking in huts where persons sleep. Compared with persons in case villages, persons in control villages more commonly reported replacing thatch roofing, and growing coffee, tomatoes, onions, and melons in agricultural plots adjacent to their homesteads. Rodent and flea control practices, knowledge of plague, distance to clinics, and most care-seeking practices were similar between persons in case villages and persons in control villages. Our findings reinforce existing plague prevention recommendations and point to potentially advantageous local interventions., (© The American Society of Tropical Medicine and Hygiene.)

Over the past two decades, the majority of human plague cases have been reported from areas in Africa, including Uganda. In an effort to develop affordable plague control methods within an integrated vector control framework, we evaluated the efficacy of indoor residual spraying (IRS) techniques commonly used for mosquito control for controlling fleas on hut-dwelling commensal rodents in a plague-endemic region of Uganda. We evaluated both the standard IRS spraying (walls and ceiling) and a modified IRS technique that included insecticide application on not only on walls and ceiling but also a portion of the floor of each treated hut. Our study demonstrated that both the standard and modified IRS applications were effective at significantly reducing the flea burden and flea infestation of commensal rodents for up to 100 d after application, suggesting that IRS could potentially provide simultaneous control of mosquito and fleaborne diseases.

Quantifying the abundance of host-seeking fleas is critical for assessing risk of human exposure to flea-borne disease agents, including Yersinia pestis, the etiological agent of plague. Yet, reliable measures of the efficacy of existing host-seeking flea collection methods are lacking. In this study, we compare the efficacy of passive and active methods for the collection of host-seeking fleas in both the laboratory and human habitations in a plague-endemic region of northwest Uganda. In the laboratory, lighted "Kilonzo" flea traps modified with either blinking lights, the creation of shadows or the generation of carbon dioxide were less efficient at collecting Xenopsylla cheopis Rothchild and Ctenocephalides felis Bouché fleas than an active collection method using white cotton socks or cotton flannel. Passive collection using Kilonzo light traps in the laboratory collected significantly more X. cheopis than C. felis and active collection, using white socks and flannel, collected significantly more C. felis than X. cheopis. In field studies conducted in Uganda, Kilonzo traps using a flashlight were similar in their collection efficacy to Kilonzo traps using kerosene lamps. However, in contrast to laboratory studies, Kilonzo flea traps using flashlights collected a greater number of fleas than swabbing. Within human habitations in Uganda, Kilonzo traps were especially useful for collecting C. felis, the dominant species found in human habitations in this area.

Plague, caused by the bacteria Yersinia pestis, is a severe, often fatal disease. This study focuses on the plague-endemic West Nile region of Uganda, where limited information is available regarding environmental and behavioral risk factors associated with plague infection. We conducted observational surveys of 10 randomly selected huts within historically classified case and control villages (four each) two times during the dry season of 2006 (N = 78 case huts and N = 80 control huts), which immediately preceded a large plague outbreak. By coupling a previously published landscape-level statistical model of plague risk with this observational survey, we were able to identify potential residence-based risk factors for plague associated with huts within historic case or control villages (e.g., distance to neighboring homestead and presence of pigs near the home) and huts within areas previously predicted as elevated risk or low risk (e.g., corn and other annual crops grown near the home, water storage in the home, and processed commercial foods stored in the home). The identified variables are consistent with current ecologic theories on plague transmission dynamics. This preliminary study serves as a foundation for future case control studies in the area.

Plague, a life-threatening flea-borne zoonosis caused by Yersinia pestis, has most commonly been reported from eastern Africa and Madagascar in recent decades. In these regions and elsewhere, prevention and control efforts are typically targeted at fine spatial scales, yet risk maps for the disease are often presented at coarse spatial resolutions that are of limited value in allocating scarce prevention and control resources. In our study, we sought to identify sub-village level remotely sensed correlates of elevated risk of human exposure to plague bacteria and to project the model across the plague-endemic West Nile region of Uganda and into neighboring regions of the Democratic Republic of Congo. Our model yielded an overall accuracy of 81%, with sensitivities and specificities of 89% and 71%, respectively. Risk was higher above 1,300 meters than below, and the remotely sensed covariates that were included in the model implied that localities that are wetter, with less vegetative growth and more bare soil during the dry month of January (when agricultural plots are typically fallow) pose an increased risk of plague case occurrence. Our results suggest that environmental and landscape features play a large part in classifying an area as ecologically conducive to plague activity. However, it is clear that future studies aimed at identifying behavioral and fine-scale ecological risk factors in the West Nile region are required to fully assess the risk of human exposure to Y. pestis.

In Uganda, the West Nile region is the primary epidemiologic focus for plague. The aims of this study were to 1) describe flea-host associations within a plague-endemic region of Uganda, 2) compare flea loads between villages with or without a history of reported human plague cases and between sampling periods, and 3) determine vector loads on small mammal hosts in domestic, peridomestic, and sylvatic settings. We report that the roof rat, Rattus rattus, is the most common rodent collected in human dwellings in each of the 10 villages within the two districts sampled. These rats were commonly infested with efficient Y. pestis vectors, Xenopsylla cheopis and X. brasiliensis in Arua and Nebbi districts, respectively. In peridomestic and sylvatic areas in both districts, the Nile rat, Arvicanthus niloticus, was the most abundant rodent and hosted the highest diversity of flea species. When significant temporal differences in flea loads were detected, they were typically lower during the dry month of January. We did not detect any significant differences in small mammal abundance or flea loads between villages with our without a history of human plague, indicating that conditions during inter-epizootic periods are similar between these areas. Future studies are needed to determine whether flea abundance or species composition changes during epizootics when humans are most at risk of exposure.

Human plague is found in the West Nile region of Uganda and Democratic Republic of the Congo where flea vectors are often found inhabiting homes. We have developed a multiplexed, real-time polymerase chain reaction assay targeting mitochondrial genes that is capable of detecting blood meal sources in fleas collected off-host in East Africa. Laboratory tests showed that the assay is specific for the intended targets and has a detection limit below one picogram of DNA. Testing of wild-caught fleas from the Democratic Republic of Congo suggests that humans are at significant risk from flea-borne disease and implicates domestic animals including cats, chickens, and the black rat as potential sources of human exposure to fleas and flea-borne diseases. Future application of the assay will help us better define the ecology of plague in East Africa to implement effective control measures to combat the spread of disease.

The West Nile region of Uganda represents an epidemiologic focus for human plague in east Africa. However, limited capacity for diagnostic laboratory testing means few clinically diagnosed cases are confirmed and the true burden of disease is undetermined. The aims of the study were 1) describe the spatial distribution of clinical plague cases in the region, 2) identify ecologic correlates of incidence, and 3) incorporate these variables into predictive models that define areas of plague risk. The model explained 74% of the incidence variation and revealed that cases were more common above 1,300 m than below. Remotely-sensed variables associated with differences in soil or vegetation were also identified as incidence predictors. The study demonstrated that plague incidence can be modeled at parish-level scale based on environmental variables and identified parishes where cases may be under-reported and enhanced surveillance and preventative measures may be implemented to decrease the burden of plague.

In recent decades, the majority of human plague cases (caused by Yersinia pestis) have been reported from Africa. In northwest Uganda, which has had recent plague outbreaks, cat fleas (Ctenocephalides felis) have been reported as the most common fleas in the home environment, which is suspected to be a major exposure site for human plague in this country. In the past, C. felis has been viewed as only a nuisance-biting insect because limited laboratory studies suggested it is incapable of transmitting Y. pestis or is an inefficient vector. Our laboratory study shows that C. felis is a competent vector of plague bacteria, but that efficiency is low compared with another flea species collected in the same area: the oriental rat flea, Xenopsylla cheopis. On the other hand, despite its low vector efficiency, C. felis is the most common flea in human habitations in a plague-endemic region of Uganda (Arua and Nebbi Districts), and occasionally infests potential rodent reservoirs of Y. pestis such as the roof rat (Rattus rattus) or the Nile rat (Arvicanthis niloticus). Plague control programs in this region should remain focused on reducing rat flea populations, although our findings imply that cat fleas should not be ignored by these programs as they could play a significant role as secondary vectors.