Clinical Features and Patient Management of Lujo Hemorrhagic Fever

<div><p>Background</p><p>In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries.</p><p>Methods and Findings</p><p>We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa.</p><p>Conclusions</p><p>Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation.</p></div

Timeline graph depiction of outbreak.

<p>Timeline graph depiction of outbreak.</p

Clinical laboratory parameters in 5 patients with Lujo hemorrhagic fever.

<p>The day of illness that the value was noted is in parentheses.</p><p>*Patients 1, 2, and 5 received transfusions of packed red blood cells, platelets, and fresh frozen plasma during the course of their illnesses.</p><p>Abbreviations: ALT-alanine aminotransferase, AST-aspartate aminotransferase, CRP-C reactive protein, ESR-erythrocyte sedimentation rate, Hb-hemoglobin, HCT-hematocrit, INR-international normalized ratio, LDH-lactate dehydrogenase, ND-not done, PCT- procalcitonin, PTT-partial thromboplastin time, WBC-white blood cell count.</p><p>Clinical laboratory parameters in 5 patients with Lujo hemorrhagic fever.</p

CT scan of the brain of Patient 5 showing cerebral edema on illness day 12.

<p>CT scan of the brain of Patient 5 showing cerebral edema on illness day 12.</p

Clinical manifestations of Lujo haemorrhagic fever in Patient 5, including facial and neck swelling (A), subconjunctival haemorrhage (B), and maculopapular rash(C).

<p>Clinical manifestations of Lujo haemorrhagic fever in Patient 5, including facial and neck swelling (A), subconjunctival haemorrhage (B), and maculopapular rash(C).</p

Clinical signs and symptoms in 5 patients with Lujo hemorrhagic fever.

<p>Signs and symptoms are listed in order of appearance during the course of infection. Only manifestations noted during the first 2 weeks of illness are shown.</p><p>Clinical signs and symptoms in 5 patients with Lujo hemorrhagic fever.</p

Evaluation of Two Influenza Surveillance Systems in South Africa

<div><p>Background</p><p>The World Health Organisation recommends outpatient influenza-like illness (ILI) and inpatient severe acute respiratory illness (SARI) surveillance. We evaluated two influenza surveillance systems in South Africa: one for ILI and another for SARI.</p><p>Methodology</p><p>The Viral Watch (VW) programme has collected virological influenza surveillance data voluntarily from patients with ILI since 1984 in private and public clinics in all 9 South African provinces. The SARI surveillance programme has collected epidemiological and virological influenza surveillance data since 2009 in public hospitals in 4 provinces by dedicated personnel. We compared nine surveillance system attributes from 2009–2012.</p><p>Results</p><p>We analysed data from 18,293 SARI patients and 9,104 ILI patients. The annual proportion of samples testing positive for influenza was higher for VW (mean 41%) than SARI (mean 8%) and generally exceeded the seasonal threshold from May to September (VW: weeks 21–40; SARI: weeks 23–39). Data quality was a major strength of SARI (most data completion measures >90%; adherence to definitions: 88–89%) and a relative weakness of the VW programme (62% of forms complete, with limited epidemiologic data collected; adherence to definitions: 65–82%). Timeliness was a relative strength of both systems (e.g. both collected >93% of all respiratory specimens within 7 days of symptom onset). ILI surveillance was more nationally representative, financially sustainable and expandable than the SARI system. Though the SARI programme is not nationally representative, the high quality and detail of SARI data collection sheds light on the local burden and epidemiology of severe influenza-associated disease.</p><p>Conclusions</p><p>To best monitor influenza in South Africa, we propose that both ILI and SARI should be under surveillance. Improving ILI surveillance will require better quality and more systematic data collection, and SARI surveillance should be expanded to be more nationally representative, even if this requires scaling back on information gathered.</p></div

Number of respiratory specimens tested by week, South Africa (2009–2012).

<p>Number of respiratory specimens tested by week, South Africa (2009–2012).</p

Characteristics of the Viral Watch and severe acute respiratory infection (SARI) surveillance programmes.

<p>* Most sentinel sites consist of private sector general practitioners, though primary care clinics, paediatric outpatient departments, and occupational health clinics are also included.</p><p>Characteristics of the Viral Watch and severe acute respiratory infection (SARI) surveillance programmes.</p

Laboratory confirmed influenza detection rates, South Africa (2009–2012)*

<p>Laboratory confirmed influenza detection rates, South Africa (2009–2012)*</p