Kerry Dierberg

Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study

BACKGROUNDnLimited data are available on the prevalence and predictors of clinical sequelae in survivors of Ebola virus disease (EVD). The EVD Survivor Clinic in Port Loko, Sierra Leone, has provided clinical care for 603 of 661 survivors living in the district. We did a cross-sectional study to describe the prevalence, nature, and predictors of three key EVD sequelae (ocular, auditory, and articular) in this cohort of EVD survivors.nnnMETHODSnWe reviewed available clinical and laboratory records of consecutive patients assessed in the clinic between March 7, 2015, and April 24, 2015. We used univariate and multiple logistic regression to examine clinical and laboratory features of acute EVD with the following outcomes in convalescence: new ocular symptoms, uveitis, auditory symptoms, and arthralgias.nnnFINDINGSnAmong 277 survivors (59% female), median age was 29 years (IQR 20-36) and median time from discharge from an EVD treatment facility to first survivor clinic visit was 121 days (82-151). Clinical sequelae were common, including arthralgias (n=210, 76%), new ocular symptoms (n=167, 60%), uveitis (n=50, 18%), and auditory symptoms (n=67, 24%). Higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time RT-PCR testing) was independently associated with uveitis (adjusted odds ratio [aOR] 3·33, 95% CI 1·87-5·91, for every five-point decrease in cycle threshold) and with new ocular symptoms or ocular diagnoses (aOR 3·04, 95% CI 1·87-4·94).nnnINTERPRETATIONnClinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of survivors of EVD and urgent provision of ocular care as part of health systems strengthening in EVD-affected west African countries.nnnFUNDINGnCanadian Institutes of Health Research.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the countrys most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIHs experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

Minimally Symptomatic Infection in an Ebola ‘Hotspot’: A Cross-Sectional Serosurvey

Introduction Evidence for minimally symptomatic Ebola virus (EBOV) infection is limited. During the 2013–16 outbreak in West Africa, it was not considered epidemiologically relevant to published models or projections of intervention effects. In order to improve our understanding of the transmission dynamics of EBOV in humans, we investigated the occurrence of minimally symptomatic EBOV infection in quarantined contacts of reported Ebola virus disease cases in a recognized ‘hotspot.’ Methodology/Principal Findings We conducted a cross-sectional serosurvey in Sukudu, Kono District, Sierra Leone, from October 2015 to January 2016. A blood sample was collected from 187 study participants, 132 negative controls (individuals with a low likelihood of previous exposure to Ebola virus), and 30 positive controls (Ebola virus disease survivors). IgG responses to Ebola glycoprotein and nucleoprotein were measured using Alpha Diagnostic International ELISA kits with plasma diluted at 1:200. Optical density was read at 450 nm (subtracting OD at 630nm to normalize well background) on a ChroMate 4300 microplate reader. A cutoff of 4.7 U/mL for the anti-GP ELISA yielded 96.7% sensitivity and 97.7% specificity in distinguishing positive and negative controls. We identified 14 seropositive individuals not known to have had Ebola virus disease. Two of the 14 seropositive individuals reported only fever during quarantine while the remaining 12 denied any signs or symptoms during quarantine. Conclusions/Significance By using ELISA to measure Zaire Ebola virus antibody concentrations, we identified a significant number of individuals with previously undetected EBOV infection in a ‘hotspot’ village in Sierra Leone, approximately one year after the village outbreak. The findings provide further evidence that Ebola, like many other viral infections, presents with a spectrum of clinical manifestations, including minimally symptomatic infection. These data also suggest that a significant portion of Ebola transmission events may have gone undetected during the outbreak. Further studies are needed to understand the potential risk of transmission and clinical sequelae in individuals with previously undetected EBOV infection.

Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015.

The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapiens-wt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus.

Hepatitis B prevalence and treatment needs among Tibetan refugees residing in India

Untreated chronic hepatitis B can lead to liver failure and/or liver cancer. These complications can be avoided through prevention with vaccination or treatment of disease. To inform health policy for the Tibetan community in India, we conducted study of hepatitis B prevalence and treatment needs. We conducted a cross‐sectional study over 3 months of 2013. Households were randomly selected for participation via a satellite map; one boarding school and one residential monastery were also included. Participants were asked questions and a whole blood sample was collected for HBsAg assay. Participants with a positive HBsAg result were tested for hepatitis B e antigen, ALT, and AST. Participants with a negative HBsAg result were tested for anti‐hepatitis B core antibodies. We recruited 2,769 participants; of which 247 (8.9%) were positive for HBsAg. Participants more likely to have a positive HBsAg result were those born in Tibet (12.4%) and aged 30–59 years old. Of those with a positive HBsAg result, 60.7% were positive for hepatitis B e antigen 7% of whom fit into a likely treatment‐needed category; the others fit into management categories requiring repeat ALT testing with or without liver fibrosis assessment. Among participants negative for HBsAg, 52.9% from household sampling had anti‐HBc antibodies. We identified a high endemicity of chronic hepatitis B in a Tibetan community in India. Resource appropriate approaches are needed for managing chronic hepatitis B in settings such as this one. J. Med. Virol. 88:1357–1363, 2016.

Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study: Reverse Transcription-Polymerase Chain Reaction and Cataract Surgery Outcomes of Ebola Survivors in Sierra Leone

Background Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. Methods We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). Findings We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P < 0.001). Interpretation EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.

Anatomy of a Hotspot: Chain and Seroepidemiology of Ebola Virus Transmission, Sukudu, Sierra Leone, 2015–16

Studies have yet to include minimally symptomatic Ebola virus (EBOV) infections and unrecognized Ebola virus disease (EVD) in Ebola-related transmission chains and epidemiologic risk estimates. We conducted a cross-sectional, sero-epidemiological survey from October 2015 to January 2016 among 221 individuals living in quarantined households from November 2014 to February 2015 during the Ebola outbreak in the village of Sukudu, Sierra Leone. Of 48 EBOV-infected persons, 25% (95% confidence interval [CI], 14%-40%) had minimally symptomatic EBOV infections and 4% (95% CI, 1%-14%) were unrecognized EVD cases. The pattern of minimally symptomatic EBOV infections in the transmission chain was nonrandom (P < .001, permutation test). Not having lived in the same house as an EVD case was significantly associated with minimally symptomatic infection. This is the first study to investigate a chain of EBOV transmission inclusive of minimally symptomatic EBOV infections and unrecognized EVD. Our findings provide new insights into Ebola transmission dynamics and quarantine practices.

Food Insecurity as a Risk Factor for Outcomes Related to Ebola Virus Disease in Kono District, Sierra Leone: A Cross-Sectional Study

Studies have shown that people suffering from food insecurity are at higher risk for infectious and noncommunicable diseases and have poorer health outcomes. No study, however, has examined the association between food insecurity and outcomes related to Ebola virus disease (EVD). We conducted a cross-sectional study in two Ebola-affected communities in Kono district, Sierra Leone, from November 2015 to September 2016. We enrolled persons who were determined to have been exposed to Ebola virus. We assessed the association of food insecurity, using an adapted version of the Household Food Insecurity Access Scale, a nine-item scale well validated across Africa, with having been diagnosed with EVD and having died of EVD, using logistic regression models with cluster-adjusted standard errors. We interviewed 326 persons who were exposed to Ebola virus; 61 (19%) were diagnosed with EVD and 45/61 (74%) died. We found high levels (87%) of food insecurity, but there was no association between food insecurity and having been diagnosed with EVD. Among EVD cases, those who were food insecure had 18.3 times the adjusted odds of death than those who were food secure (P = 0.03). This is the first study to demonstrate a potential relationship between food insecurity and having died of EVD, although larger prospective studies are needed to confirm these findings.

Strengthening the Free Healthcare Initiative through a pharmacy and supply chain intervention: Partners in Health's experience in rural Sierra Leone

Abstract Background To improve high maternal and under-5 mortality—among the worst globally—Sierra Leones Ministry of Health and Sanitation (MOHS) enacted the Free Healthcare Initiative in 2010. Under this initiative, pregnant and lactating women and children aged younger than 5 years receive medical treatment and essential medicines free of charge at public facilities. However, the availability of medicines remains inconsistent, which results in patients paying for medicines and an undermining of the quality of care and trust in the health-care system. These gaps between services and medicines promised under the Free Healthcare Initiative and actual resources delivered worsened during the 2013–15 Ebola epidemic, which strained an already weak health-care system. Here, we describe an approach to strengthen pharmacy and supply chain systems to improve access to essential medicines at a district hospital in Sierra Leone. Methods In 2015, Partners In Health undertook a gap analysis to understand the barriers to drug availability for patients eligible for the Free Healthcare Initiative at Koidu Government Hospital (KGH). A multidisciplinary task force identified priorities and created a partnership with the MOHS. Partners In Healths Director of Pharmacy led meetings with hospital management, shadowed clinical staff, and performed an inventory of drugs and medical supplies. Findings The gap analysis revealed challenges in the areas of human resources, infrastructure, storage, and information systems. The results led to the following interventions: decentralisation of medication distribution from hospital to ward level; the hiring of four pharmacy technicians; expansion of central warehousing; and implementation of electronic reporting tools to improve consumption data. MOHS pharmacy staff were mentored to improve feedback mechanisms between central and district levels. Between November, 2015, and August, 2016, these changes resulted in nearly 100% availability of essential drugs—with 80% provided via the strengthened MOHS system—and elimination of out-of-pocket expenses for patients. Additionally, trust in the public health-care system has improved: compared with a 2012 and 2013 pre-Ebola baseline at KGH, paediatric and maternity admissions have increased by 47%, with a 95% increase in hospital-based deliveries. Interpretation The success of the Free Healthcare Initiative is rooted in its shared ownership with the MOHS and the integration of central-level and district-level information systems. The approach described here could be used to guide new interventions to strengthen pharmacy supply chains elsewhere in Sierra Leone and other low-resource settings. Funding Partners In Health, Sierra Leone.