Viruses associated with acute febrile illness in Africa cause a spectrum of clinical disease from mild to life-threatening. Routine diagnostic methods are insufficient to identify all viral pathogens in this region. In this study, 1281 febrile Ugandan patients were prospectively recruited as part of the CDC-UVRI Acute Febrile Illness Study and pre-screened for common pathogens. 210/1281 undiagnosed samples, and 20 additional samples from viral outbreaks were subjected to metagenomic sequencing. Viral pathogens were identified in 44/230 (19%), including respiratory, hepatitis, blood-borne, gastrointestinal and vector-borne viruses. Importantly, one case of Crimean-Congo haemorrhagic fever and two cases each of Rift Valley fever, dengue and yellow fever were detected in 7/230 (3%) of cases. Le Dantec virus, last reported in 1969, was also identified in one patient. The presence of high-consequence and (re-)emerging viruses of public health concern highlights the need for enhanced population-based diagnostic surveillance in the African region.

Between April and November 2023, 27 unexplained human deaths that presented with swelling of the arms, skin sores with black centers, difficulty in breathing, obstructed swallowing, headaches, and other body aches were reported in Kyotera District, Uganda by the Public Health Emergency Operations Center. Subsequently, the death of cattle on farms and the consumption of carcass meat by some residents were also reported. Field response teams collected clinical/epidemiological data and autopsy samples to determine the cause of deaths. Metagenomic next-generation sequencing (mNGS) and target enrichment sequencing conducted on postmortem samples confirmed Bacillus anthracis, the etiological agent of anthrax disease, as the cause of the deaths. Applying mNGS to autopsy specimens is useful as a retrospective tool for identifying high-consequence pathogens during suspected outbreaks of unknown etiology.

Objectives:Utilizing post-mortem examination for routine monitoring of infectious diseases and pandemic preparedness is a common-sense, yet uncommon, public health measure. Here, we established a novel mortuary surveillance program in Uganda that leverages the unbiased nature of metagenomic next-generation sequencing (mNGS) to detect pathogens in recently deceased individuals. Methods:Between October 2022 and December 2023, specimens and patient metadata were collected from 2,607 individuals across five mortuary sites around Kampala. Specimens were pre-screened for hemorrhagic fever viruses by RT-qPCR and a subset (n = 134) of RT-qPCR negatives were sequenced by mNGS. Results:A variety of DNA (herpes, parvovirus, bufavirus) and RNA (Saffold, Salivirus, HAV) viruses, vectored (Bartonella, Rickettsia) and nosocomial (Enterobacter, Klebsiella) bacterial infections, and potentially lethal respiratory pathogens (e.g., Cryptococcus neoformans, Corynebacterium diphtheria) were detected. A localized outbreak of Enterovirus B (EV-B), specifically a recombinant Echovirus E7, was observed in Kampala. An epidemiologic assessment indicated that most identified pathogens were acquired via direct and/or indirect contact (e.g., fecal-oral, fomites) and that other modes of transmission (e.g., food-borne, insect-vectored) played a less significant role. Conclusion:Integration of mortuary surveillance, coupled with mNGS, into public health systems represents a powerful strategy for identifying unrecognized outbreaks and monitoring the (re-) emergence of infectious diseases.

In April 2023, an outbreak of acute hepatitis was reported amongst internally displaced persons in the Nazareth community of South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis.

HIV-1 is characterized by remarkable genetic diversity resulting from its high replication rate, error-prone reverse transcriptase enzyme and recombination events. In Uganda, HIV-1 subtype diversity is mostly dominated by subtypes A, D, and A1/D Unique Recombinant Forms (URFs). In this study, deep sequences of HIV from patients with known antiretroviral therapy (ART) status were analyzed to determine the subtypes and to identify drug-resistance mutations circulating in the study population. Of the 187 participant samples processed for next-generation sequencing (NGS), 137 (73%) were successfully classified. The majority of HIV-1 strains were classified as subtype A (75, 55%), D (43, 31%), with other subtypes including C (3, 2%), A1/D (9, 7%) and CRF10_CD (1, <1%). Recombinant analysis of nine complete A1/D HIV genomes identified novel recombination patterns described herein. Furthermore, we report for the first time in Uganda, an HIV-1 CRF10_CD strain from a fisherfolk in a Lake Victoria Island fishing community.

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda.

Mpox is a zoonotic disease caused by the monkeypox virus. We report on human mpox cases in Uganda identified by PCR and confirmed by deep sequencing. Phylogenetic analysis revealed clustering with other clade Ib sequences associated with recent outbreaks in the Democratic Republic of the Congo.

SUMMARY Background Viruses that cause acute febrile illness (AFI) in sub-Saharan Africa cause a spectrum of disease from mild to life-threatening. Viral infection is often undiagnosed, as routine diagnostics are insufficient to capture the diversity of circulating pathogens. Methods 1281 patients with fever of 2-7 days were prospectively recruited from three sites in Uganda as part of the CDC-UVRI AFI Study and screened with enhanced diagnostics. Plasma from 233 undiagnosed patients was analysed using metagenomic next-generation sequencing (mNGS). Confirmatory testing was carried out by PCR and serology. Findings Thirty-eight viral pathogens were identified by mNGS in 35/233 (15%) undiagnosed patients including Measles, Hepatitis A/B/E viruses, Human immunodeficiency virus-1, Rhinovirus, Rotavirus-like virus, Human herpesvirus 6B, Human parainfluenza virus 3 and Enteroviruses. Four high-consequence arboviruses were found in six patients; Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus, dengue virus and yellow fever virus. Le Dantec virus, last reported in 1969, was detected and confirmed by serology in one patient (and a contact of that patient). The majority of patients (23/30; 76%) diagnosed with an acute viral infection were treated with antibiotics and/or (12/30; 40%) antimalarials. Interpretation AFI in Uganda is commonly associated with undiagnosed viral infection, including high-consequence and rarely reported viruses. This highlights an ongoing risk to public health and the need for improved vigilance. MNGS alongside diagnostic serology is a powerful method for clinical surveillance to investigate circulating viral pathogens. Cost-effective diagnostic assays should be adapted according to regional needs for testing. Funding Medical Research Council and Wellcome Trust

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

Objective The objective of this study was to evaluate the performance of seven antigen rapid diagnostic tests (Ag RDTs) in a clinical setting to identify those that could be recommended for use in the diagnosis of SARS-CoV-2 infection in Uganda. Methods This was a cross-sectional prospective study. Nasopharyngeal swabs were collected consecutively from COVID-19 PCR positive and COVID-19 PCR negative participants at isolation centers and points of entry, and tested with the SARS-CoV-2 Ag RDTs. Test sensitivity and specificity were generated by comparing results against qRT-PCR results (Berlin Protocol) at a cycle threshold (Ct) cut-off of ≤39. Sensitivity was also calculated at Ct cut-offs ≤29 and ≤33. Results None of the Ag RDTs had a sensitivity of ≥80% at Ct cut-off values ≤33 and ≤39. Two kits, Panbio ™ COVID-19 Ag and VivaDiag ™ SARS-CoV-2 Ag had a sensitivity of ≥80% at a Ct cut-off value of ≤29. Four kits: BIOCREDIT COVID -19 Ag, COVID-19 Ag Respi-Strip, MEDsan ® SARS-CoV-2 Antigen Rapid Test and Panbio ™ COVID-19 Ag Rapid Test had a specificity of ≥97%. Conclusions This evaluation identified one Ag RDT, Panbio ™ COVID-19 Ag with a performance at high viral load (Ct value ≤29) reaching that recommended by WHO. This kit was recommended for screening of patients with COVID -19-like symptoms presenting at health facilities.

Uganda is highly vulnerable to public health emergencies (PHEs) due to its geographic location next to the Congo Basin epidemic hot spot, placement within multiple epidemic belts, high population growth rates, and refugee influx. In view of this, Uganda's Ministry of Health established the Public Health Emergency Operations Center (PHEOC) in September 2013, as a central coordination unit for all PHEs in the country. Uganda followed the World Health Organization's framework to establish the PHEOC, including establishing a steering committee, acquiring legal authority, developing emergency response plans, and developing a concept of operations. The same framework governs the PHEOC's daily activities. Between January 2014 and December 2021, Uganda's PHEOC coordinated response to 271 PHEs, hosted 207 emergency coordination meetings, trained all core staff in public health emergency management principles, participated in 21 simulation exercises, coordinated Uganda's Global Health Security Agenda activities, established 6 subnational PHEOCs, and strengthened the capacity of 7 countries in public health emergency management. In this article, we discuss the following lessons learned: PHEOCs are key in PHE coordination and thus mitigate the associated adverse impacts; although the functions of a PHEOC may be legalized by the existence of a National Institute of Public Health, their establishment may precede formally securing the legal framework; staff may learn public health emergency management principles on the job; involvement of leaders and health partners is crucial to the success of a public health emergency management program; subnational PHEOCs are resourceful in mounting regional responses to PHEs; and service on the PHE Strategic Committee may be voluntary.

IntroductionSerological testing is needed to better understand the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Rapid diagnostic tests (RDTs) have been developed to detect specific antibodies, IgM and IgG, to the virus. The performance of 25 of these RDTs was evaluated.MethodsA serological reference panel of 50 positive and 100 negative plasma specimens was developed from SARS-CoV-2 PCR and antibody positive patients and pre-pandemic SARS-CoV-2-negative specimens collected in 2016. Test performance of the 25 RDTs was evaluated against this panel.ResultsA total of 10 RDTs had a sensitivity ≥98%, while 13 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Four RDTs (Boson, MultiG, Standard Q, and VivaDiag) had both sensitivity and specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Only three RDTs had a sensitivity ≥98%, while 10 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgM antibodies. Three RDTs (Autobio, MultiG, and Standard Q) had sensitivity and specificity ≥98% to combined IgG/IgM. The RDTs that performed well also had perfect or almost perfect inter-reader agreement.ConclusionsThis evaluation identified three RDTs with a sensitivity and specificity to IgM/IgG antibodies of ≥98% with the potential for widespread antibody testing in Uganda.

BackgroundPrior to the first recorded outbreak of Rift Valley fever (RVF) in Uganda, in March 2016, earlier studies done until the 1970's indicated the presence of the RVF virus (RVFV) in the country, without any recorded outbreaks in either man or animals. While severe outbreaks of RVF occurred in the neighboring countries, none were reported in Uganda despite forecasts that placed some parts of Uganda at similar risk.The Ministry of Agriculture, Animal Industry and Fisheries (MAAIF) undertook studies to determine the RVF sero-prevalence in risk prone areas.Three datasets from cattle sheep and goats were obtained; one from retrospective samples collected in 2010-2011 from the northern region; the second from the western region in 2013 while the third was from a cross-sectional survey done in 2016 in the south-western region. Laboratory analysis involved the use of the Enzyme Linked Immunosorbent Assays (ELISA). Data were subjected to descriptive statistical analyses, including non-parametric chi-square tests for comparisons between districts and species in the regions.ResultsDuring the Yellow Fever outbreak investigation of 2010-2011 in the northern region, a total sero-prevalence of 6.7% was obtained for anti RVFV reacting antibodies (IgG and IgM) among the domestic ruminant population. The 2013 sero-survey in the western region showed a prevalence of 18.6% in cattle and 2.3% in small ruminants. The 2016 sero-survey in the districts of Kabale, Kanungu, Kasese, Kisoro and Rubirizi, in the south-western region, had the respective district RVF sero-prevalence of 16.0, 2.1, 0.8, 15.1and 2.7% among the domestic ruminants combined for this region; bovines exhibited the highest cumulative sero-prevalence of 15.2%, compared to 5.3 and 4.0% respectively for sheep and goats per species for the region.ConclusionsThe absence of apparent outbreaks in Uganda, despite neighboring enzootic areas, having minimal restrictions to the exchange of livestock and their products across borders, suggest an unexpected RVF activity in the study areas that needs to be unraveled. Therefore, more in-depth studies are planned to mitigate the risk of an overt RVF outbreak in humans and animals as has occurred in neighboring countries.

On April 20, 2018, the Kween District Health Office in Kween District, Uganda reported 7 suspected cases of human anthrax. A team from the Uganda Ministry of Health and partners investigated and identified 49 cases, 3 confirmed and 46 suspected; no deaths were reported. Multiple exposures from handling the carcass of a cow that had died suddenly were significantly associated with cutaneous anthrax, whereas eating meat from that cow was associated with gastrointestinal anthrax. Eating undercooked meat was significantly associated with gastrointestinal anthrax, but boiling the meat for >60 minutes was protective. We recommended providing postexposure antimicrobial prophylaxis for all exposed persons, vaccinating healthy livestock in the area, educating farmers to safely dispose of animal carcasses, and avoiding handling or eating meat from livestock that died of unknown causes.

INTRODUCTION:Gastrointestinal anthrax is a rare but serious disease. In August 2017, Isingiro District, Uganda reported a cluster of >40 persons with acute-onset gastroenteritis. Symptoms included bloody diarrhoea. We investigated to identify the etiology and exposures, and to inform control measures.METHODS:We defined a suspected case as acute-onset of diarrhoea or vomiting during 15-31 August 2017 in a resident (aged≥2 years) of Kabingo sub-county, Isingiro District; a confirmed case was a suspected case with a clinical sample positive for Bacillus anthracis by culture or PCR. We conducted descriptive epidemiology to generate hypotheses. In a case-control study, we compared exposures between case-patients and neighbourhood-matched controls. We used conditional logistic regression to compute matched odds ratios (MOR) for associations of illness with exposures.RESULTS:We identified 61 cases (58 suspected and 3 confirmed; no deaths). In the case-control study, 82% of 50 case-patients and 12% of 100 controls ate beef purchased exclusively from butchery X during the week before illness onset (MOR = 46, 95%CI = 4.7-446); 8.0% of case-patients and 3.0% of controls ate beef purchased from butchery X and elsewhere (MOR = 19, 95%CI = 1.0-328), compared with 6.0% of case-patients and 30% of controls who did not eat beef. B. anthracis was identified in two vomitus and one stool sample. Butchery X slaughtered a sick cow and sold the beef during case-patients' incubation period.CONCLUSION:This gastrointestinal anthrax outbreak occurred due to eating beef from butchery X. We recommended health education, safe disposal of the carcasses of livestock or game animals, and anthrax vaccination for livestock.

ObjectivesThere is a high demand for SARS-CoV-2 testing to identify COVID-19 cases. Real-time quantitative PCR (qRT-PCR) is the recommended diagnostic test but a number of constraints prevent its widespread implementation, including cost. The aim of this study was to evaluate a low cost and easy to use rapid antigen test for diagnosing COVID-19 at the point of care.MethodsNasopharyngeal swabs from suspected COVID-19 cases and low-risk volunteers were tested with the STANDARD Q COVID-19 Ag Test and the results were compared with the qRT-PCR results.ResultsIn total, 262 samples were collected, including 90 qRT-PCR positives. The majority of samples were from males (89%) with a mean age of 34 years and only 13 (14%) of the positives were mildly symptomatic. The sensitivity and specificity of the antigen test were 70.0% (95% confidence interval (CI): 60–79) and 92% (95% CI: 87–96), respectively, and the diagnostic accuracy was 84% (95% CI: 79–88). The antigen test was more likely to be positive for samples with qRT-PCR Ct values ≤29, with a sensitivity of 92%.ConclusionsThe STANDARD Q COVID-19 Ag Test performed less than optimally in this evaluation. However, the test may still have an important role to play early in infection when timely access to molecular testing is not available but the results should be confirmed by qRT-PCR.

INTRODUCTION:The World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated. METHODS:In total 11 blood based and 3 oral transudate kits were evaluated. All together 2746 participants from seven sites, covering the four different regions of Uganda participated. Two enzyme immunoassays (EIAs) run in parallel were used as the gold standard. The performance and cost of the different algorithms was calculated, with a pre-determined price cut-off of either cheaper or within 20% price of the current algorithm of Determine + Statpak + Unigold. In the second phase, the three best algorithms selected in phase I were used at the point of care for purposes of quality control using finger stick whole blood. RESULTS:We identified three algorithms; Determine + SD Bioline + Statpak; Determine + Statpak + SD Bioline, both with the same sensitivity and specificity of 99.2% and 99.1% respectively and Determine + Statpak + Insti, with sensitivity and specificity of 99.1% and 99% respectively as having performed better and met the cost requirements. There were 15 other algorithms that performed better than the current one but rated more than the 20% price. None of the 3 oral mucosal transudate kits were suitable for inclusion in an algorithm because of their low sensitivities. Band intensity affected the performance of individual RTs but not the final algorithms. CONCLUSION:We have come up with three algorithms we recommend for public or Government procurement based on accuracy and cost. In case one algorithm is preferred, we recommend to replace Unigold, the current tie breaker with SD Bioline. We further recommend that all the 18 algorithms that have shown better performance than the current one are made available to the private sector where cost may not be a limiting factor.

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.

BACKGROUND:With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). METHODS:We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. RESULTS:Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥ 70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count < 250 cells/μl (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥ 100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14). CONCLUSION:Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda.