Catherine Houlihan

Caring for Critically Ill Patients with Ebola Virus Disease. Perspectives from West Africa

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.

Human papillomavirus infection and increased risk of HIV acquisition. A systematic review and meta-analysis

Objectives:Human papillomavirus (HPV), one of the commonest sexually transmitted infections, may be a cofactor in HIV acquisition. We systematically reviewed the evidence for an association of HPV infection with HIV acquisition in women, heterosexual men and men who have sex with men (MSM). Design:Systematic review and meta-analysis. Methods:Studies meeting inclusion criteria in Pubmed, Embase and conference abstracts up to 29 July 2011 were identified. Random effects meta-analyses were performed to calculate summary hazard ratios (HR). Publication bias and statistical heterogeneity were evaluated and population attributable fractions (PAFs) calculated. Results:Eight articles were included, with previously unpublished data from five authors. Seven studies found an association between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women doubled with prevalent HPV infection with any genotype [HR = 2.06 (95% CI = 1.44–2.94), I2 = 0%], although adjustment for confounders was often inadequate. The effect was similar for high-risk [HR = 1.99 (95% CI = 1.54–2.56), I2 = 8.4%] and low-risk [HR = 2.01 (95% CI = 1.27–3.20), I2 = 0%] HPV genotypes with weak evidence of publication bias (P = 0.06). Two studies in men were identified: both showed an association between HPV infection and HIV acquisition. Unpublished data from one of two studies in women indicated an association between genotypes targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to infection with any HPV genotype ranged between 21 and 37%. Conclusion:If further studies validate the association between HPV infection and HIV acquisition, HPV vaccines may reduce HIV incidence in high HPV prevalence populations, in addition to preventing cervical cancer. HIV surveillance studies during implementation of HPV vaccine programmes are warranted.

Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study

BACKGROUND Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. METHODS We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. FINDINGS 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. INTERPRETATION Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. FUNDING None.

Being ready to treat Ebola virus disease patients.

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD.

Persistent Zika Virus Detection in Semen in a Traveler Returning to the United Kingdom from Brazil, 2016.

Zika virus is normally transmitted by mosquitos, but cases of sexual transmission have been reported. We describe a patient with symptomatic Zika virus infection in whom the virus was detected in semen for 92 days. Our findings support recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection.

Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus

BACKGROUND The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact. METHODS We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies. FINDINGS The assay had a specificity of 100% (95% CI 98·9-100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8-98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1-20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2-4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level. INTERPRETATION This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions. FUNDING Wellcome Trust ERAES Programme, Save the Children.

Life threatening infections labelled swine flu

Algorithms for remote diagnosis and issue of antiviral drugs are indispensable during a pandemic.1 Their application through the National Pandemic Flu Service to both high and low prevalence areas is, however, controversial, and the lack of specificity in the use of the algorithm has been highlighted by Payne et al and at November’s …

Prevalence of Human Papillomavirus in Adolescent Girls Before Reported Sexual Debut

Background. Human papillomavirus (HPV) vaccines are recommended for girls prior to sexual debut because they are most effective if administered before girls acquire HPV. Little research has been done on HPV prevalence in girls who report not having passed sexual debut in high HPV-prevalence countries. Methods. Using attendance registers of randomly selected primary schools in the Mwanza region of Tanzania, we enrolled girls aged 15–16 years who reported not having passed sexual debut. A face-to-face interview on sexual behavior and intravaginal practices, and a nurse-assisted self-administered vaginal swab were performed. Swabs were tested for 13 high-risk and 24 low-risk HPV genotypes. Results. HPV was detected in 40/474 (8.4%; 95% confidence interval [CI], 5.9–11.0) girls. Ten different high-risk and 21 different low-risk genotypes were detected. High-risk genotypes were detected in 5.3% (95% CI, 3.5–7.8). In multivariable analysis, only intravaginal cleansing (practiced by 20.9%) was associated with HPV detection (adjusted odds ratio = 2.19, 95% CI, 1.09–4.39). Conclusion. This cohort of adolescent Tanzanian girls had a high HPV prevalence prior to self-reported sexual debut, and this was associated with intravaginal cleansing. This most likely reflects underreporting of sexual activity, and it is possible that intravaginal cleansing is a marker for unreported sexual debut or nonpenetrative sexual behaviors.

Rapid acquisition of HPV around the time of sexual debut in adolescent girls in Tanzania.

Abstract Background: No reports exist on genotype-specific human papillomavirus (HPV) acquisition in girls after first sex in sub-Saharan Africa, despite high HPV prevalence and cervical cancer incidence. Methods: We followed 503 HP-unvaccinated girls aged 15-16 years in Mwanza, Tanzania, 3-monthly for 18 months with interviews and self-administered vaginal swabs. Swabs were tested for 13 higHRisk and 24 low-risk HPV genotypes. Incidence, clearance and duration of overall HPV and genotype-specific infections were calculated and associated factors evaluated. Results : A total of 106 participants reported first sex prior to enrolment ( N = 29) or during follow-up (N = 77). One was HIV-positive at the final visit. The remaining 105 girls contributed 323 adequate specimens. Incidence of any new HPV genotype was 225/100 person-years (pys), and incidence of vaccine types HPV-6, -11, -16 and -18 were 12, 2, 2 and 7/100 pys, respectively. Reporting sex in the past 3 months and knowing the most recent sexual partner for a longer period before sex were associated with HPV acquisition. Median time from reported sexual debut to first HPVinfection was 5 months, and infection duration was 6 months. Conclusion: This is the first description of HPV acquisition after first sex in sub-Saharan Africa where the incidence of cervical cancer is amongst the highest in the world. HPV incidence was very high after first sex, including some vaccine genotypes, and infection duration was short. This very high HPV incidence may help explain high cervical cancer rates, and supports recommendations that the HPV vaccine should be given to girls before first sex.

Ebola exposure, illness experience, and Ebola antibody prevalence in international responders to the West African Ebola epidemic 2014–2016: A cross-sectional study

Background Healthcare and other front-line workers are at particular risk of infection with Ebola virus (EBOV). Despite the large-scale deployment of international responders, few cases of Ebola virus disease have been diagnosed in this group. Since asymptomatic or pauci-symptomatic infection has been described, it is plausible that infections have occurred in healthcare workers but have escaped being diagnosed. We aimed to assess the prevalence of asymptomatic or pauci-symptomatic infection, and of exposure events, among returned responders to the West African Ebola epidemic 2014–2016. Methods and findings We used snowball sampling to identify responders who had returned to the UK or Ireland, and used an online consent and questionnaire to determine their exposure to EBOV and their experience of illness. Oral fluid collection devices were sent and returned by post, and samples were tested using an EBOV IgG capture assay that detects IgG to Ebola glycoprotein. Blood was collected from returnees with reactive samples for further testing. Unexposed UK controls were also recruited. In all, 300 individuals consented, of whom 268 (89.3%) returned an oral fluid sample (OFS). The majority had worked in Sierra Leone in clinical, laboratory, research, and other roles. Fifty-three UK controls consented and provided samples using the same method. Of the returnees, 47 (17.5%) reported that they had had a possible EBOV exposure. Based on their free-text descriptions, using a published risk assessment method, we classified 43 (16%) as having had incidents with risk of Ebola transmission, including five intermediate-risk and one high-risk exposure. Of the returnees, 57 (21%) reported a febrile or diarrhoeal illness in West Africa or within 1 mo of return, of whom 40 (70%) were not tested at the time for EBOV infection. Of the 268 OFSs, 266 were unreactive. Two returnees, who did not experience an illness in West Africa or on return, had OFSs that were reactive on the EBOV IgG capture assay, with similar results on plasma. One individual had no further positive test results; the other had a positive result on a double-antigen bridging assay but not on a competitive assay or on an indirect EBOV IgG ELISA. All 53 controls had non-reactive OFSs. While the participants were not a random sample of returnees, the number participating was high. Conclusions This is the first study, to our knowledge, of the prevalence of EBOV infection in international responders. More than 99% had clear negative results. Sera from two individuals had discordant results on the different assays; both were negative on the competitive assay, suggesting that prior infection was unlikely. The finding that a significant proportion experienced “near miss” exposure events, and that most of those who experienced symptoms did not get tested for EBOV at the time, suggests a need to review and standardise protocols for the management of possible exposure to EBOV, and for the management of illness, across organisations that deploy staff to outbreaks.