2018
Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.
Published in: Clin Infect Dis. 2018;66(4):594-603.
Background Global data on durability of first-line antiretroviral therapy (ART) in children with HIV is limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.
Methods Children <18-years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitor (NRTI) plus non-NRTI (NNRTI) or boosted-protease inhibitor (PI)) were included. Switch to second-line was defined as: (i) change across drug class (PI to NNRTI or vice versa) or within PI-class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss-to-follow-up as competing risks.
Results Of 3,668 children included, median [IQR] age at ART initiation was 6.1 [1.7,10.5] years. Initial regimens were 32% PI, 34% nevirapine (NVP), 33% efavirenz-based. Median duration of follow-up from ART start was 5.4 [2.9,8.3] years. Cumulative incidence of switch at 5 years was 21% (95% CI 20, 23), with lowest incidence in Russia/Ukraine and highest in UK/Ireland. Median time to switch was 30 [15, 58] months, two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load at ART start, and NVP-based initial regimens were associated with increased risk of switch. Among those switched, 65% had viral load <400c/mL at 12-months after start of second-line ART.
Conclusions One in five children switched to second-line by 5 years of ART, with two-thirds failure related. Advanced HIV, older age and NVP-based regimens were associated with increased risk of switch.
2018
Authors: Soriano-Arandes A, Rivero-Calle I, Nastouli E, et al.
Published in: Expert Rev Anti Infect Ther. 2018;16(3):243-254
Introduction: Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed.
Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms [‘Zika’] AND [‘Perinatal Infection’] OR [‘Congenital Infection’] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study.
Expert commentary: ZIKV is a new teratogenic/neurotropic virus affecting fetuses. Many challenges are still far from being solved regarding the epidemiology, case definition, clinical and laboratory diagnosis, and preventive measures. An approach using ‘omics’ and new biomarkers for diagnosis, and a ZIKV-vaccine for treatment, might finally give us the tools to solve these challenges.
2018
Authors: Zangari P, Palma P, Cotugno N, et al.
Published in: J Virus Erad.2018;4: 51–54
Abstract: The first EPIICAL General Assembly meeting was held in an atmosphere of growing optimism. Many novel and exciting proposals for HIV research studies were discussed and are described above. The consortium aims to maintain this integrated developmental research on NDMTs, from predictive platforms to proof-of-concept studies, through the excellent collaborative effort made during the first 18 months of EPIICAL, some of which is described in this report. The emphasis on an innovative research platform is unique and may lead to optimisation of the management of perinatally HIV-infected children. Collectively, the updates and the discussions from the General Assembly attest to the benefit of nurturing an international collaborative effort on paediatric HIV research and confirm that EPIICAL is successfully on track.
2017
Authors: Rinaldi S, Cotugno N, Pallikkuth S, Palma P, Pahwa S; on behalf of the EPIICAL Consortium
Published: 8th Conference on HIV Persistence
Background Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children provides an opportunity to limit the size of reservoir, but whether and how the time of ART treatment initiation can durably impact host immune responses associated with HIV infection is still unknown. In this study, we analyzed HIV-specific CD4 T cell functionality in vertically HIV-infected children in whom ART was initiated early or late after birth.
2017
Authors: Luck SE, Wieringa JW, Blazquez-Gamero D, et al.
Published in: Pediatr Infect Dis J. 2017;36(12):1205-1213
2017
Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.
Published in: Eur J Clin Pharmacol. 2017;73(4):463-468
Background Zidovudine (ZDV) has been associated with risk of haematological toxicity. Safety data from clinical trials is generally limited to 48 weeks. We assessed the short- and mid-term toxicity of ZDV/lamivudine (3TC) fixed-dose combination scored tablets in HIV-infected children followed in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) network.
Methods Fourteen cohorts provided data on patients <18 years of age taking ZDV/3TC scored tablets between 2008 and 2012. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory adverse events (AEs) for hepatobiliary and haematological disorders were estimated by duration on drug (<12, 12–24, >24 months). Clinical adverse events and reasons for tablet discontinuation were described.
Results Of 541 patients on ZDV/3TC, 388 (72%) had weight and dose data available, of whom 350 (90%) weighed ≥14 kg and were eligible for tablet use; 161 (41%) were aged <10 years on an approved dose, 189 (49%) aged ≥10 years on an approved dose, and 30 (8%) were on an unapproved dose. Median age at ZDV/3TC start was 10 years, and 79% had taken ART previously (60% had prior exposure to ZDV/3TC). Overall rates of grade ≥3 AEs for absolute neutrophil counts, bilirubin, haemoglobin, platelet counts, white blood cell counts (WBC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were ≤2/100 person years (PY) for patients taking approved doses. Two hundred thirty-three (43%) patients were not on ZDV/3TC tablets at most recent follow-up; a small number (17 (7%)) discontinued due to AEs (17 (7%)), and the most common reason for discontinuation was treatment simplification (73 (31%)).
Conclusions Scored ZDV/3TC tablets, both approved and taken off-label, appear to be well tolerated with few side effects. Few patients discontinued treatment due to toxicity. As ZDV/3TC tablets are taken with other antiretrovirals, it is difficult to infer association between toxicities and specific agents, highlighting the importance of widening long-term pharmacovigilance to a broader spectrum of drug combinations.
2017
Authors: Bernays S, Paparini S, Seeley J, Namukwaya Kihika S, Gibb D, Rhodes T.
Published in: BMJ Open. 2017;7(2):e012934
Objectives A qualitative study of the BREATHER (PENTA 16) randomised clinical trial, which compared virological control of Short Cycle Therapy (SCT) (5 days on: 2 days off) with continuous efavirenz (EFV)-based antiretroviral therapy (CT) in children and young people (aged 8–24) living with HIV with viral load <50 c/mL to examine adaptation, acceptability and experience of SCT to inform intervention development.
Setting Paediatric HIV clinics in the UK (2), Ireland (1), the USA (1) and Uganda (1).
Participants All BREATHER trial participants who were over the age of 10 and aware of their HIV diagnosis were invited to participate. 49 young people from both arms of the BREATHER trial (31 females and 18 males; 40% of the total trial population in the respective sites; age range 11–24) gave additional consent to participate in the qualitative study.
Results Young people from both trial arms had initial concerns about the impact of SCT on their health and adherence, but these decreased over the early months in the trial. Young people randomised to SCT reported preference for SCT compared with CT pre-trial. Attitudes to SCT did not vary greatly by gender or country. Once short-term adaptation challenges were overcome, SCT was positively described as reducing impact of side effects, easing the pressure to carry and remember medication and enabling more weekend social activities. Young people on both arms reported frequent medication side effects and occasional missed doses that they had rarely voiced to clinical staff. Participants liked SCT by trial end but were concerned that peers who had most problems adhering could find SCT disruptive and difficult to manage.
Conclusions To realise the potential of SCT (and mitigate possible risks of longer interruptions), careful dissemination and communication post-trial is needed. SCT should be provided alongside a package of monitoring, support and education over 3 months to allow adaptation.
2017
Authors: Namukwaya S, Paparini S, Seeley J, Bernays S.
Published in: Front Public Health. 2017;5:343.
Abstract: Despite great advances in pediatric HIV care, rates and the extent of full disclosure of HIV status to infected children remain low especially in resource-constrained setting. The World Health Organisation recommends that, by the age of 10-12 years old, children should be made fully aware of their HIV-positive status. However, this awareness is often delayed until much later in their adolescence. Few studies have been conducted to investigate what influences caregivers’ decision-making process in this regard in low-income settings. In this article, we present an analysis of care dyads of caregivers and HIV-positive young people in Kampala, Uganda, as part of the findings of a longitudinal qualitative study about young people’s adherence to antiretroviral therapy embedded in an international clinical trial (BREATHER). Repeat in-depth interviews were conducted with 26 young people living with HIV throughout the course of the trial, and once-off interviews with 16 of their caregivers were also carried out toward the end of the trial. In this article, we examine why and how caregivers decide to disclose a young person’s HIV status to them and explore their feelings and dilemmas toward disclosure, as well as how young people reacted and the influence it had on their relationships with and attitudes toward their caregivers. Caregivers feared the consequences of disclosing the young person’s positive status to them and disclosure commonly occurred hurriedly in response to a crisis, rather than as part of an anticipated and planned process. A key impediment to disclosure was that caregivers feared that disclosing would damage their relationships with the young people and commonly used this as a reason to continue to postpone disclosure. However, young people did not report prolonged feelings of blame or anger toward their caregivers about their own infection, but they did express frustration at the delay and obfuscation surrounding the disclosure process. Our findings can inform the ways in which mainstream HIV services support caregivers through the disclosure process. This includes providing positive encouragement to disclose fully and to be more confident in initiating and sustaining the timely process of disclosure.
2017
Authors: Hakim J, Musiime V, Szubert AJ; REALITY Trial Team
Published in: N Engl J Med. 2017;377(3):233-245
Background In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.
Methods In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality.
ResultsA total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.
Conclusions Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects.
2017
Authors: Theys K, Libin P, Dallmeier K, et al.
Published in: PLoS Pathog. 2017;13(9):e1006528
In this letter, the authors address the need for curation and standardized annotation of ZIKV reference genomes in order to guide researchers and clinicians in genomic analyses and the translation of research findings.
2017
Authors: James-Powell T, Brown Y, Christie CDC, et al.
Published in: West Indian Med J, 2017; 66:10-19
2017
Authors: Halai UA, Nielsen-Saines K, Moreira ME, et al.
Published in: Clin Infect Dis. 2017;65(6):877-883
2017
Authors: Sáfadi MA, Nascimento-Carvalho CM
Published in: Pediatr Infect Dis J.2017;36(3):333-336
Abstract After remaining related to few sporadic cases in limited regions for more than half century since its discovery, Zika virus (ZIKV) was recently introduced into the Western Hemisphere, first in Brazil and then spreading very rapidly in the Americas. Unexpectedly, an increased incidence of microcephaly and other neurologic malformations in fetuses born to mothers infected with ZIKV during pregnancy was reported in Brazil, leading the World Health Organization to declare this situation a Public Health Emergency of International Concern
2017
Authors: Garcez PP, Nascimento JM, de Vasconcelos JM, et al.
Published in: Sci Rep. 2017 Jan 23;7:40780
Abstract Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
2017
Authors: Sacramento CQ, de Melo GR, de Freitas CS, et al.
Published in: Sci Rep.2017 Jan 18;7: 40920
Abstract Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.
2017
Authors: Gaskell KM, Houlihan C, Nastouli E, Checkly AM
Published in: Emerg Infect Dis.2017;23(1):137-139
Abstract 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.
2017
Authors: Melbourne-Chambers R., Christie CD, Greenaway E., Bullock R
Published in: West Indian Med J.2016;65(3):425-430
Abstract Dengue, Chikungunya Fever (CHIKV) and Zika virus (ZIKV) are all transmitted by the Aedes aegypti mosquito and are currently circulating in Jamaica. Jamaica has been experiencing a ZIKV epidemic since February 2016. At the University Hospital of the West Indies (UHWI), Kingston, Jamaica, a cluster of five cases of paralysis attributed to neuro-inflammation was noted amongst adolescents admitted to the institution. Three were diagnosed with acute myelitis and one each with acute disseminated encephalomyelitis (ADEM) and guillain barre syndrome (GBS). In these patients, there were common presenting symptoms, characteristic findings of peripheral nerve involvement and a history of contact with persons with symptoms of possible ZIKV in the majority. In only one case was a viral association, Dengue infection, confirmed. This case series suggests a unique clinical pattern of neuro-inflammation in Jamaican adolescents occurring during the ZIKV epidemic and questions the role of the three circulating arboviruses in the pathogenesis.
2017
Authors: Iovine NM, Lednicky J, Cherabuddi K, et al.
Published in: Clin Infect Dis. 2017;64(1): 72–75.
Abstract Zika virus and dengue virus serotype 2 were isolated from a patient with travel to Haiti who developed fever, rash, arthralgias, and conjunctivitis. The infecting Zika virus was related to Venezuelan and Brazilian strains but evolved along a lineage originating from strains isolated in 2014 in the same region of Haiti.
2017
Authors: Fuller TL, Calvet G, Genaro Estevam C, et al.
Published in: PLoS One. 2017;12(11):e0188002
Abstract: The burden of arboviruses in the Americas is high and may result in long-term sequelae with infants disabled by Zika virus infection (ZIKV) and arthritis caused by infection with Chikungunya virus (CHIKV). We aimed to identify environmental drivers of arbovirus epidemics to predict where the next epidemics will occur and prioritize municipalities for vector control and eventual vaccination. We screened sera and urine samples (n = 10,459) from residents of 48 municipalities in the state of Rio de Janeiro for CHIKV, dengue virus (DENV), and ZIKV by molecular PCR diagnostics. Further, we assessed the spatial pattern of arbovirus incidence at the municipal and neighborhood scales and the timing of epidemics and major rainfall events. Lab-confirmed cases included 1,717 infections with ZIKV (43.8%) and 2,170 with CHIKV (55.4%) and only 29 (<1%) with DENV. ZIKV incidence was greater in neighborhoods with little access to municipal water infrastructure (r = -0.47, p = 1.2×10-8). CHIKV incidence was weakly correlated with urbanization (r = 0.2, p = 0.02). Rains began in October 2015 and were followed one month later by the largest wave of ZIKV epidemic. ZIKV cases markedly declined in February 2016, which coincided with the start of a CHIKV outbreak. Rainfall predicted ZIKV and CHIKV with a lead time of 3 weeks each time. The association between rainfall and epidemics reflects vector ecology as the larval stages of Aedes aegypti require pools of water to develop. The temporal dynamics of ZIKV and CHIKV may be explained by the shorter incubation period of the viruses in the mosquito vector; 2 days for CHIKV versus 10 days for ZIKV.
2017
Authors: Donà D, Luise D, Da Dalt L, Giaquinto C.
Published in: Int J Pediatr; 2017: 4239268.
Abstract: Background. Pneumonia represents an important threat to children’s health in both developed and developing countries. In the last 10 years, many national and international guidelines on the treatment of pediatric CAP have been published, in order to optimize the prescription of antibiotics and limit their cost and side effects. However, the practical implementation of these guidelines is still limited. Main Text. We analyzed the current recommendations for the therapy of pediatric community-acquired pneumonia (CAP) that all converge on the identification of aminopenicillins and beta-lactams as the optimal treatment for CAP. We also conducted a review of the current literature on antibiotic regimens used for pediatric CAP to identify the current state of guidelines implementation in different settings. We selected 37 studies published from 2010 to 2016, including both retrospective and prospective studies, mainly cross-sectional and hospital based. The results show a global heterogeneity in the antibiotics prescription for pediatric CAP, with application of guidelines varying from 0% to more than 91% and with important differences even within the same country. Conclusions. Our review has demonstrated that the implementation of the guidelines is still limited but also that achieving the optimal prescription is possible and can be done in both developed and developing countries.
2017
Authors: Schalkwijk S, Colbers A, Konopnicki D, et al.
Published in: Clin Infect Dis. 2017; 65(8):1335-1341.
2017
Authors: Judd A, Lodwick R, Noguera-Julian A, et al.. Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord.
Published in: HIV Med. 2017;18(3):171-180
Objectives The aim of the study was to determine the time to, and risk factors for, triple‐class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection.
Methods We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV‐1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI.
Results The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre‐ART AIDS, NNRTI‐based initial regimens, higher pre‐ART viral load and lower pre‐ART CD4.
Conclusions The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development
2017
Authors: Nelson B, Melbourne-Chambers R, Christie CDC
Published in: West Indian Med J. Published Online: December 20, 2017
Abstract Zika Virus is neurotropic. We report two children from the Caribbean island of Grenada, a three-year-old with acute neuro-inflammation who had intractable seizures, meningo-encephalitis, CSF pleocytosis and Zika IgM positive acute serology and a four-year-old with acute demyelinating encephalomyelitis manifesting as generalized seizures, optic neuritis, diffuse cerebral dysfunction, encephalopathy, impaired speech and ataxia who also had CSF pleocytosis as well as Zika IgM and dengue IgM positive acute serologies. Both cases occurred during the 2016 Zika and Dengue fever epidemic in Grenada. Both children recovered completely. The etiologic role of the Zika and Dengue arboviruses is discussed.
2017
Authors: Schwarz ER
Published in: Curr Opin Virol. 2017;27:71-77
Abstract Measles, mumps, and rubella have recently taken the stage as re-emerging diseases of public health importance-particularly in regards to the consequences seen with perinatal infections. Effective vaccination strategies have successfully reduced the spread of measles, mumps, and rubella in the United States, but a current trend of increased vaccination hesitancy, fear of vaccine safety, and spread of misconceptions surrounding the science of vaccines have led to a relative resurgence of these diseases in the developed world. This article aims to explore why measles, mumps, and rubella should continue to be on the radar of medical professionals, and why the study of these diseases is important for understanding other teratogenic viruses of public health importance.
2017
Authors: da Silva IRF, Frontera JA, Bispo de Filippis AM, Nascimento OJMD
Published in: JAMA Neurol.2017;74(10):1190-1198
Importance There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.
Objective To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis.
Design, Setting, and Participants A prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.
Interventions Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase–polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected.
Main Outcomes and Measures The detection of neurologic complications secondary to ZIKV infection.
Results Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5).
Conclusions and Relevance In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.
2017
Authors: Bosch I, de Puig H, Hiley M, et al.
Published in: Sci Transl Med. 2017 Sep 27;9(409)
Abstract The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1–4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1–4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction–positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.
2017
Authors: Barreto-Vieira DF, Jacome FC, da Silva MAN, et al.
Published in: PLoS One. 2017;12(9):e0184397
Abstract Zika virus (ZIKV) is a member of the flavivirus genus, and its genome is approximately 10.8 kilobases of positive-strand RNA enclosed in a capsid and surrounded by a membrane. Studies on the replication dynamics of ZIKV are scarce, which limits the development of antiviral agents and vaccines directed against ZIKV. In this study, Aedes albopictus mosquito lineage cells (C6/36 cells) and African green monkey kidney epithelial cells (Vero cells) were inoculated with a ZIKV sample isolated from a Brazilian patient, and the infection was characterized by immunofluorescence staining, phase contrast light microscopy, transmission electron microscopy and real-time RT-PCR. The infection was observed in both cell lineages, and ZIKV particles were observed inside lysosomes, the rough endoplasmic reticulum and viroplasm-like structures. The susceptibility of C6/36 and Vero cells to ZIKV infection was demonstrated. Moreover, this study showed that part of the replicative cycle may occur within viroplasm-like structures, which has not been previously demonstrated in other flaviviruses.
2017
Authors: Balmaseda A, Stettler K, Medialdea-Carrera R, et al.
Published in: Proc Natl Acad Sci U S A. 2017;114(31):8384-8389
Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/ plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n = 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENVnaive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.
2017
Authors: Braga JU, Bressan C, Dalvi APR, et al.
Published in: PLoS One.2017;12(6):e0179725.
Background Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barrésyndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic.
Methodology We evaluated the accuracy of various Zika case definitions in a scenario where Dengue and Chikungunya viruses co-circulate. Signs and symptoms that best discriminated PCR confirmed Zika from other laboratory confirmed febrile or exanthematic diseases were identified to propose and test predictive models for Zika infection based on these clinical features.
Results and discussion Our derived score prediction model had the best performance because it demonstrated the highest sensitivity and specificity, 86·6% and 78·3%, respectively. This Zika case definition also had the highest values for auROC (0·903) and R2 (0·417), and the lowest Brier score 0·096.
Conclusions In areas where multiple arboviruses circulate, the presence of rash with pruritus or conjunctival hyperemia, without any other general clinical manifestations such as fever, petechia or anorexia is the best Zika case definition.
2017
Authors: Nascimento OJM, Frontera JA, Amitrano DA, Bispo de Filippis AM, Da Silva IRF; RIO-GBS-ZIKV Research Group
Published in: Neurology 2017;88(24):2330-2332
2017
Authors: Palma P, Chan M, Goodall R, Judd A, Gibb D, Babiker A, Rojo P.
Published: 35th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), May 23rd-27th May, 2017, Madrid
Background A major obstacle to curing HIV infection is persistence of virus as integrated proviral DNA in long-lived cells even after many years on ART. ART-free HIV remission is more likely to occur if viral suppression is achieved very early in infection. We investigated factors associated with time to virological suppression in early ART treated children from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).
2017
Authors: Palma P, Zangari P, Cotugno N, Rocca S, Nastouli E, McCoy LE, Ferns RB, Pahwa S, Rossi P
Published: 24th Conference on Retroviruses and Opportunistic Infections, February 13th – 16th, 2017, Seattle. P_1975.
Background It is still unknown whether the paucity of HIV-specific immune responses in early-treated (treated within 6 months of age; ET) HIV-infected children may represent a limitation or an advantage in the perspective of immune therapeutic studies. In ET patients, the failure to develop an immune response is attributed to the lack of antigen (Ag) stimulation, possibly indicating shrinking HIV reservoirs (Luzuriaga, JID 2014). Analysis of HIV antibodies (Ab) can reveal important insights to characterizing host immune profiles associated with HIV remission which appears to be linked with different serological profiles (Burbelo, JID 2014). Recent findings showed a functional plasticity of memory B-cell compartment, suggesting that IgM memory B-cells during a primary stage of infection share specific memory characteristics with IgG memory B-cells. The role of IgM memory responses in humans is debated (Seifert, PNAS 2015). Their generation, in the context of short-term Ag persistence such as in ET HIV-infected children, has been poorly investigated. Our aim was to further dissect Bcell responses in ET patients with different HIV Ab profiles and relate those to the predicted size of HIV reservoir (Total HIV-DNA) and to immune memory B-cell response.
2017
Authors: Colbers A, Schalkwijk S, Konopnicki D, Gingelmaier A, Lambert J, van der Ende I, Moltó J, Burger D.
Published: 24th Conference on Retroviruses and Opportunistic Infections, February 13th – 16th, 2017 – Seattle. Abstract number 754.
2017
Authors: Bernays S, Paparini S, Seeley J, Rhodes T.
Published in: Med Anthropol. 2017;36(5):485-499.
Abstract: Global health priorities are being set to address questions on adherence to HIV antiretroviral therapy in adolescence. Few studies have explored young people’s perspectives on the complex host of social and relational challenges they face in dealing with their treatment in secret and their condition in silence. In redressing this, we present findings from a longitudinal qualitative study with young people living with HIV in the UK, Ireland, US, and Uganda, embedded within the BREATHER international clinical trial. Drawing from Goffman’s notion of stigma, we analyze relational dynamics in HIV clinics, as rare spaces where HIV is “known,” and how young people’s relationships may be threatened by non-adherence to treatment. Young people’s reflections on and strategies for maintaining their reputation as patients raise questions about particular forms of medicalization of HIV and the moralization of treatment adherence that affect them, and how these may restrict opportunities for care across the epidemic.
2017
Authors: Hinkula J, Petkov S, Ljungberg K, Hallengärd D, Bråve A, Isaguliants M, Falkeborn T, Sharma S, Liakina V, Robb M, Eller M, Moss B, Biberfeld G, Sandström E, Nilsson C, Markland K, Blomberg P, Wahren B.
Published in: Heliyon
2017
Authors: Schomaker M, Leroy V, Wolfs T, et al. On behalf of theIeDEA West and Southern Africa regional collaborations and COHERE in EuroCoord.
Published in: Int J Epidemiol. 2017;46(2):453-465.
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.
Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula.
Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3(394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes.
Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
2017
Authors: Volynets G, Skyortsowa TA, Ptapov AS, et al.
Published in: EASL, 19th – 23rd April 2017, Amsterdam
2017
Authors: Thorne C, Turkova A, Indolfi G, Venturini E, Giaquinto C
Published in: AIDS. 2017;31(1):127-135.
Objective To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment.
Design Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts.
Methods Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol.
Results Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4 cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV.
Conclusion The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.
2017
Authors: Majekodunmi AO, Thorne C, Malyuta R, et al.
Published in: Pediatr Infect Dis J. 2017;36(5):e123-e129
Objective To compare CD4 T cell recovery in HIV/HCV coinfected children with recovery in HIV monoinfected children.
Method We studied 355 HIV monoinfected and 46 HIV/HCV coinfected children receiving antiretroviral therapy (ART) during a median follow-up period of 4.2 years (interquartile range: 2.7-5.3 years). Our dataset came from the Ukraine pediatric HIV Cohort and the HIV/HCV coinfection study within the European Pregnancy and Paediatric HIV Cohort Collaboration. We fitted an asymptotic nonlinear mixed-effects model of CD4 T cell reconstitution to age-standardized CD4 counts in all 401 children and investigated factors predicting the speed and extent of recovery.
Results We found no significant impact of HCV coinfection on either pre-ART or long-term age-adjusted CD4 counts (z scores). However, the rate of increase in CD4 z score was slower in HIV/HCV coinfected children when compared with their monoinfected counterparts (P < 0.001). Both monoinfected and coinfected children starting ART at younger ages had higher pre-ART (P < 0.001) and long-term (P < 0.001) CD4 z scores than those who started when they were older.
Conclusions HIV/HCV coinfected children receiving ART had slower CD4 T cell recovery than HIV monoinfected children. HIV/HCV coinfection had no impact on pre-ART or long-term CD4 z scores. Early treatment of HIV/HCV coinfected children with ART should be encouraged.
2017
Authors: Indolfi G, Thorne C, El-Sayed MH, Giaquinto C, Gonzalez-Peralta RP.
Published in: J Pediatr Gastroenterol Nutr. 2017;64(6):851-854
Abstract The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children.
2017
Authors:
Published in: Pediatr Infect Dis J. 2017 May;36(5):e123-e129. doi: 10.1097/INF.0000000000001478. PMID: 28403051; PMCID: PMC5380220.
2016
Authors: Colbers A, Best B, Schalkwijk S, et al. PANNA Network and the IMPAACT 1026 Study Team.
Published in: Clin Pharmacokinet. 2016;55(3):381-96
Abstract Pregnant women are usually excluded from clinical trials. Physiologically based pharmacokinetic (PBPK) modelling may provide a method to predict pharmacokinetics in pregnant women, without the need to perform extensive in vivo clinical trials. Here, we used mechanistic modelling to delineate the potential impact of drug transporters on darunavir pharmacokinetics and to identify current knowledge gaps that limit accurate PBPK modelling of darunavir/ritonavir (darunavir/r) exposure in pregnancy. Simcyp (version 13.2) was used for PBPK modelling, using physicochemical and in vitro pharmacokinetic parameters of darunavir and ritonavir from the literature. The Michaelis-Menten constant (K m) and the maximum rate of metabolite formation (V max) for cytochrome P450 3A4-mediated darunavir biotransformation and inhibition by ritonavir were determined experimentally, while the contributions of hepatocyte influx and efflux transporters were assessed by sensitivity analysis. The simulations were compared with previously published clinical pharmacokinetic data. We found that use of a well-stirred liver model overestimated darunavir exposure substantially. A permeability-limited liver model, including hepatic uptake and efflux transporters and an efficient enterohepatic circulation step, resulted in an acceptable description of darunavir/r exposure. For the 600/100 mg darunavir/r twice-daily dose and the 800/100 mg once-daily dose, the estimated pharmacokinetic parameters were within a 2-fold range of the reported data. The predicted decreases in the area under the concentration-time curve (AUC) values during pregnancy for the twice- and once-daily doses were 27 and 41%, respectively, which were in line with the observed decreases of 17-22 and 33%. In conclusion, our data support a clinically relevant role of hepatic transporters in darunavir pharmacokinetics. By including them in our model, we successfully approximated the increase in darunavir exposure mediated by ritonavir co-administration and the decrease in darunavir exposure observed during pregnancy.
2016
Authors: Ramos-Martin R , Johnson A, Livermore J, et al.
Published in: J Antimicrob Ther 2016;71(4):992-1002
2016
Authors: Bailey H, Malyuta R, Townsend C, Cortina Borja M, Thorne C for the Ukraine European Collaborative Study in EuroCoord.
Published in: Reprod Health. 2016;22(3):13-27.
Background Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe.
Methods Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV-positive women at delivery and between 1 and 12 months postpartum. Depressive symptoms in the previous month were assessed using a self-report screening tool. Other data collected included demographics, antiretroviral therapy (ART)-related self-efficacy, and perceptions of risks/benefits of interventions to prevent mother-to-child transmission (PMTCT). Characteristics of women with and without a positive depression screening test result were compared using Fisher’s exact test and χ2 test for categorical variables.
Results A quarter (27% (49/180) antenatally and 25% (57/228) postnatally) of participants screened positive for depressive symptoms. Antenatal risk factors were living alone (58% (7/12) vs. 25% (42/167) p = 0.02), being somewhat/terribly bothered by ART side effects (40% (17/43) vs. 23% (30/129) not /only slightly bothered, p = 0.05) and having lower ART-related self-efficacy (43% (12/28) vs. 23% (25/110) with higher self-efficacy, p = 0.05). Postnatally, single mothers were more likely to screen positive (44% (20/45) vs. 21% (18/84) of cohabiting and 19% (19/99) of married women, p < 0.01) as were those unsure of the effectiveness of neonatal prophylaxis (40% (20/45) vs. 18% (28/154) sure of effectiveness, p < 0.01), those worried that neonatal prophylaxis could harm the baby (30% (44/146) vs. 14% (10/73) not worried p < 0.01) and those not confident to ask for help with taking ART (48% (11/23) vs. 27% (10/37) fairly confident and 15 % (4/26) confident that they could do this). Of women who reported wanting help for their depressive symptoms, 82% (37/45) postnatally but only 31% (12/39) antenatally were already accessing peer counselling, treatment adherence programmes, support groups or social services.
Conclusions A quarter of women screened positive for depression. Results highlight the need for proactive strategies to identify depressive symptoms, and an unmet need for provision of mental health support in the perinatal period for HIV-positive women in Ukraine.
2016
Authors: Safadi MA
Published in: Amer J Perinatol.2016; 33(11): 1029-1031
Abstract Zika virus (ZIKV) is an emerging arthropod-borne, enveloped RNA virus of the Flaviviridae family, which belongs to the genus Flavivirus, related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Two major lineages, African and Asian, have been identified through phylogenetic analyses.
2016
Authors: Davidson T., Vickers I., Christie CD
Published in: West Indian Med J 2016;65(3);442-449
Background Dengue fever is hyper-endemic in Jamaica with exponential rates of infection in successive outbreaks. The absence of local data and the potential for massive outbreaks in a country where a third of the population are children formed the basis for this study.
Methods We evaluated the outcome of dengue in children hospitalized at the University Hospital of the West Indies (UHWI), Mona, Jamaica, during the island-wide dengue fever epidemic of 2012. This retrospective study reports all physician-diagnosed cases of dengue in hospitalized children aged less than 15 years.
Results A total of 134 hospitalized children with physician-diagnosed dengue were included. One hundred and eighteen (88%) had a confirmatory dengue laboratory test. One hundred and twenty (90%) were uncomplicated and 14 (10%) had severe dengue. Severe disease was significantly associated with a longer duration between disease onset and hospital admission (p = 0.0076). Main co-morbidities were sickle cell disease (14%) and asthma (13%), however neither was associated with increased mortality. Duration of hospitalization was longer for patients with sickle cell disease. Children with short stature were significantly more likely to have severe dengue [Z-score height-for-age < 2.0; OR 6.46(1.61, 25.88), p = 0.016]. There were five deaths with a case fatality rate of 3.73%. Prior use of Non-steroidal Anti-inflammatory Drugs was documented in four deaths.
Conclusion Delayed presentation and short stature were significantly associated with severe dengue. Children with sickle cell disease had longer hospital stay. The case fatality rate was 3.73%. Use of safe and efficacious dengue vaccines should mitigate the effects of dengue-attributable childhood morbidity and mortality.
2016
Authors: Christie CD, Melbourne-Chambers R, Ennevor J, et al.
Published in: West Indian Med J 2016;65(3);431-437
Background Chikungunya virus entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica.
Methods This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22.
Results The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of cases were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 0–20 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths.
Conclusion The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.
2016
Authors: Webster-Kerr K, Christie CDC, Grant A, et al.
Published in: West Indian Med J. 2016;65(1):243-249
Background Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response.
Methods The Ministry of Health’s preparedness included: heightened surveillance, clinical management guidance, vector control and management, laboratory capacity strengthening, training and staffing, risk communication and public education, social mobilization, inter-sectoral collaboration, resource mobilization and international cooperation.
Results The first case of ZIKV was confirmed on 29 January 2016 with date of onset of 17 January 2016. From 3 January to 30 July 2016 (Epidemiological Week (EW) 1-30), 4648 cases of ZIKV were recorded (4576 suspected, 72 laboratory-confirmed). Leading symptoms were similar among suspected and confirmed cases: rash (71% and 88%), fever (65% and 53%) and joint pains (47% and 38%). There were 17 suspected cases of Guillain-Barre Syndrome. Three hundred and eighty-three were reported in pregnant women, with no reports of microcephaly to date. Zika and dengue viruses were circulating predominantly in 2016. At EW30, 1744 cases of dengue were recorded (1661 suspected and 83 confirmed). Dengue serotypes 3 and 4 circulating with 121 reports of dengue haemorrhagic fever.
2016
Authors: Oliveira DB, Almeida FJ, Durigon EL, et al.
Published in: N Engl J Med. 2016. 22;375(12):1202-4
The presence of Zika virus (ZIKV) infection has been associated with microcephaly in multiple studies, although little is known about ZIKV shedding in congenitally infected infants. We report a case of a newborn who had continued viremia with ZIKV for at least 67 days after birth.
2016
Authors: Christie CD, Giaquinto C
Published in: West Indian Med J.2016;65(1):239-242
Abstract Zika virus epidemic now involves 72 countries, worldwide. Transmission is multimodal through mosquito bites and blood and body fluids. Zika virus causes Guillain Barre Syndrome syndrome and pregnancy complications including perinatal microcephaly. Diagnosis is complicated by subclinical infection in 80%, co-circulation with dengue and chikungunya fevers with similar presentations and cross-reactivity in serological tests. There is no cure, or preventive vaccine. Large population-based studies will help to elucidate ZIKV epidemiology, vertical transmission, risks to the fetus of maternal ZIKV infection and natural history of congenital and non-congenital ZIKV infection as provided by the activities in the “ZIKAction” research consortium in Latin America, Europe and the Caribbean, which was recently funded by the European Commission.