Matthew J. Cummings

Hepatitis E in Karamoja, Uganda, 2009-2012: epidemiology and challenges to control in a setting of semi-nomadic pastoralism.

BACKGROUND A prolonged hepatitis E outbreak occurred between 2009 and 2012 among a semi-nomadic pastoralist population in the Karamoja region of Uganda. As data on the public health problems of nomadic pastoralists in sub-Saharan Africa is limited, we sought to characterize the epidemiology and challenges to control of hepatitis E in such a setting. METHODS A retrospective case-series investigation was undertaken. Surveillance line-lists of suspected hepatitis E cases maintained during the outbreak were analyzed. Standardized interviews and focus group discussions were conducted with key informants involved in outbreak control activities. RESULTS Between August 2009 and September 2012, 987 hepatitis E cases with individual case-based data were identified. Of 22 total deaths, almost half occurred during the first 4 months of the outbreak. Infection attack rates were higher among males and young adults. The average time between onset of jaundice and presentation was approximately 1 week. Challenges to control were related to persistent consumption of untreated water, poor sanitation infrastructure, remote geography, nomadic movement and civil insecurity. CONCLUSIONS The hepatitis E outbreak in Karamoja highlights the emergence of sanitation and hygiene-related disease among semi-nomadic pastoralist populations. Improving sanitation and safe water access and extending health education programs to remote pastoralist communities is crucial to prevent such diseases from becoming endemic.

Emerging and reemerging epidemic-prone diseases among settling nomadic pastoralists in Uganda

Epidemic-prone diseases have traditionally been uncommon among nomadic pastoralists as mobility allows already dispersed populations to migrate away from epidemic threats. In the Karamoja region of Uganda, nomadic pastoralists are transitioning to an increasingly settled lifestyle due to cattle raiding and associated civil insecurity. In attempts to reduce conflict in the region, the Ugandan government has instituted disarmament campaigns and encouraged sedentism in place of mobility. In Karamoja, this transition to sedentism has contributed to the emergence and reemergence of epidemic-prone diseases such as cholera, hepatitis E, yellow fever, and meningococcal meningitis. The incidence of these diseases remains difficult to measure and several challenges exist to their control. Challenges to communicable disease surveillance and control among settling nomadic pastoralists are related to nomadic mobility, remote geography, vaccination and immunity, and poor sanitation and safe water access. In addition to improving gaps in infrastructure, attracting well-trained government health workers to Karamoja and similar areas with longstanding human resource limitations is critical to address the challenges to epidemic-prone disease surveillance and control among settling nomadic pastoralists. In conjunction with government health workers, community health teams provide a sustainable method by which public health programs can be improved in the austere environments inhabited by mobile and settling pastoralists.

Dynamics of influenza in tropical Africa: Temperature, humidity, and co-circulating (sub)types

The association of influenza with meteorological variables in tropical climates remains controversial. Here, we investigate the impact of weather conditions on influenza in the tropics and factors that may contribute to this uncertainty.

Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda

Abstract Background Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.

Emergence, Epidemiology, and Transmission Dynamics of 2009 Pandemic A/H1N1 Influenza in Kampala, Uganda, 2009–2015

In sub-Saharan Africa, little is known about the epidemiology of pandemic-prone influenza viruses in urban settings. Using data from a prospective sentinel surveillance network, we characterized the emergence, epidemiology, and transmission dynamics of 2009 pandemic A/H1N1 influenza (H1N1pdm09) in Kampala, Uganda. After virus introduction via international air travel from England in June 2009, we estimated the basic reproductive number in Kampala to be 1.06-1.13, corresponding to attack rates of 12-22%. We subsequently identified 613 cases of influenza in Kampala from 2009 to 2015, of which 191 (31.2%) were infected with H1N1pdm09. Patients infected with H1N1pdm09 were more likely to be older adult (ages 35-64) males with illness onset during rainy season months. Urban settings in sub-Saharan Africa are vulnerable to importation and intense transmission of pandemic-prone influenza viruses. Enhanced surveillance and influenza pandemic preparedness in these settings is needed.

Vital signs: the first step in prevention and management of critical illness in resource-limited settings

We read with great interest the article by Dr. Riviello and colleagues highlighting the underappreciated burden and largely undefined epidemiology of acute respiratory distress syndrome (ARDS) in resource-limited settings [1]. We fully agree that initiatives to improve recognition of ARDS in such settings are urgently needed, both to facilitate the implementation of feasible therapies and guide the development of context-specific clinical and translational investigations. However, we also believe there is an opportunity to improve care and survival from severe respiratory distress and related critical illness in resource-limited settings with tools that are available now. At present, the majority of patients with severe respiratory distress in low-income countries, particularly those in sub-Saharan Africa, remain cared for on hospital wards not only as a result of limited intensive care facilities but because of under-recognition of severe illness in general. As we have observed while working as clinicians and researchers on such wards in Uganda, early identification of evolving critical illness remains challenged by infrequent vital sign monitoring and lack of standardized management practices for patients with severe respiratory distress and sepsis syndromes, a leading cause of ARDS in resource-limited settings [1, 2]. As prompt recognition and aggressive treatment of early clinical deterioration can often prevent illness progression and death, there remains an ongoing need for the development, validation, and implementation of basic triage tools to systematically guide identification and emergent treatment of severely ill patients in such settings. One such tool that is available now is the “Quick Check” protocol included in the World Health Organization’s Integrated Management of Adolescent and Adult Illness (IMAI) District Clinician Manual. Available as a standalone wall chart and accessible through mobile phone platforms, the “Quick Check” offers clinicians in austere environments a rapid, standardized approach to triage and initial management for patients arriving to the health facility [3]. In the “Quick Check,” for example, all patients with severe respiratory distress are to be placed on supplemental oxygen while vital signs are collected and indications for other emergent therapies are evaluated (e.g., empiric antimicrobials for patients with fever and judicious volume resuscitation for those with concomitant shock) [3]. In addition, recent data from Uganda suggest that “early warning” scores, which allocate points for derangements in vital signs and mental status, can be applied at the bedside to identify hospitalized patients at high risk for decompensation and death from sepsis and other severe illness, thereby providing opportunities for similar targeted interventions [4, 5]. As a result of work done by Dr. Riviello and colleagues, our understanding of the global impact of ARDS and other critical illness continues to improve. As it does, we must remain focused on the need to bolster implementation of basic monitoring measures and interventions to improve outcomes now for the sickest patients in the most resource-limited settings.

Transmission dynamics of influenza in two major cities of Uganda

In this paper, we report the epidemic characteristics of the three co-circulating influenza viruses (i.e., A/H1N1, A/H3N2, and B) in two tropical African cities-Kampala and Entebbe, Uganda-over an eight-year period (2008-2015). Using wavelet methods, we show that influenza epidemics recurred annually during the study period. In most months, two or more influenza viruses co-circulated at the same time. However, the epidemic timing differed by influenza (sub)type. Influenza A/H3N2 caused epidemics approximately every 2 years in both cities and tended to alternate with A/H1N1 or B. Influenza A/H1N1 and B produced smaller but more frequent epidemics and biennial epidemics of these two viruses tended to be synchronous. In addition, epidemics of A/H3N2 were more synchronized in the two cities (located ca.37 km apart) than that of A/H1N1 or influenza B.

The sixth vital sign: HIV status assessment and severe illness triage in Uganda

Setting: Four in-patient health facilities in western Uganda. Objective: To determine the impact of an innovative multi-modal quality improvement program on human immunodeficiency virus (HIV) status assessment and the impact of HIV status on severe illness conditions and mortality. Design: This was a staggered, pre-post quasi-experimental study designed to assess a multi-modal intervention (collaborative improvement meetings, audit and feedback, clinical mentoring) for improving quality of care following formal training in the management of severe illness in low-income settings. Results: From August 2014 to May 2015, 5759 patients were hospitalized, of whom 2451 (42.6%) had their HIV status assessed; 395 (16.1%) were HIV-infected. HIV-infected patients were significantly more likely to meet criteria for shock (27.5% vs. 15.1%, risk ratio [RR] 1.8, 95% confidence interval [CI] 1.7-1.9, P < 0.001) and severe respiratory distress (6.7% vs. 4.3%, RR 1.5, 95%CI 1.2-2.0, P < 0.001), and were significantly more likely to die in hospital (12.0% vs. 2.9%, RR 4.1, 95%CI 3.2-5.4, P < 0.001). There was no evidence of improved HIV status assessment during the intervention period (36.5% vs. 44.8%, +8.3%, 95%CI -8.3 to 24.8, P = 0.33). Conclusions: Hospitalized HIV-infected patients in western Uganda are at high risk for severe illness and death. Novel quality improvement strategies are needed to enhance hospital-based HIV testing in high-burden settings.

Unfinished business: severe acute respiratory infection in sub-Saharan Africa.

Dear Editor, We read with interest the results of the Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI), which provide valuable insight into the epidemiology and management of critically ill SARI patients in North and South America, Europe, and Asia [1]. As the authors acknowledge, the study population was limited to patients in intensive care units in highand middle-income countries. Specifically, there were no study sites in sub-Saharan Africa, a large, geographically distinct region that accounts for a substantial proportion of global mortality from acute respiratory infections and hosts several emerging infectious disease “hotspots” [2]. Although surveillance for influenza-associated severe respiratory infections in sub-Saharan Africa has expanded considerably over the past decade, the contribution of other viral and bacterial pathogens to SARIrelated hospitalizations and deaths in the region remains unclear [3]. As available data suggest that influenza-negative SARI cases in sub-Saharan Africa may experience higher mortality, increased capacity for multiplexed respiratory diagnostics is urgently needed to support molecular epidemiologic studies in the region and enhance global health security through surveillance for emerging and re-emerging pathogens [3]. In developed countries, IC-GLOSSARI and similar studies have identified populations at risk for poor outcomes from influenza and other severe respiratory infections [1]. In contrast, little is known about the clinical epidemiology of patients at highest risk for SARI-related morbidity and mortality in sub-Saharan Africa and whether co-morbidities highly prevalent in the region, namely HIV infection, tuberculosis, and malaria, are consistently associated with poor outcomes [3]. Closing such data gaps is imperative, both to develop targeted vaccination and clinical management guidelines and inform pandemic preparedness through resource-allocation planning. Finally, in their editorial accompanying the publication of IC-GLOSSARI, Dr. Martin-Loeches and colleagues highlight clinical limitations of the broad SARI case-definition but acknowledge its potential utility as a triage tool in low-income countries [4]. We believe this is an important point that deserves emphasis. In subSaharan Africa, where intensive care facilities are scarce, patients with severe respiratory infections are predominantly cared for on hospital wards where poorly standardized triage practices challenge prompt identification and treatment of critical illness [5]. However, at four sentinel surveillance sites in Uganda, we have observed health care workers translating SARI case-identification into syndromic management, with hospitalized patients meeting SARI case-definitions prioritized for further evaluation (pulse oximetry, chest radiography) and basic, emergent interventions (supplemental oxygen, anti-microbials). While epidemiologic studies and improvements in diagnostic capacity are ongoing, we believe that utilization of SARI case-definitions has potential to improve clinical management and outcomes now for severely ill patients in sub-Saharan Africa and other resource-limited settings.