Rachel B. Eidex

Case of Yellow Fever Vaccine-associated Viscerotropic Disease with Prolonged Viremia, Robust Adaptive Immune Responses, and Polymorphisms in CCR5 and RANTES Genes

BACKGROUND The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines. Despite its excellent safety record, some cases of viscerotropic adverse events develop, which are sometimes fatal. The mechanisms underlying such events remain a mystery. Here, we present an analysis of the immunologic and genetic factors driving disease in a 64-year-old male who developed viscerotropic symptoms. METHODS We obtained clinical, serologic, virologic, immunologic and genetic data on this case patient. RESULTS Viral RNA was detected in the blood 33 days after vaccination, in contrast to the expected clearance of virus by day 7 after vaccination in healthy vaccinees. Vaccination induced robust antigen-specific T and B cell responses, which suggested that persistent virus was not due to adaptive immunity of suboptimal magnitude. The genes encoding OAS1, OAS2, TLR3, and DC-SIGN, which mediate antiviral innate immunity, were wild type. However, there were heterozygous genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES, which influence the migration of effector T cells and CD14+CD16bright monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14+CD16bright monocytes in the blood during viremia and even several months after virus clearance. CONCLUSION In this patient, viscerotropic disease was not due to the impaired magnitude of adaptive immunity but instead to anomalies in the innate immune system and a possible disruption of the CCR5-RANTES axis.

Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease

Abstract Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a rare complication of yellow fever (YF) vaccination. A previously healthy 22-year-old female died following YF vaccination despite aggressive measures. Serial viral load titers, cytokine levels and host genetic factors were evaluated in an attempt to understand this unusual and lethal outcome. The patients high-titer vaccine viremia and possibly related minor genetic anomalies provide clues to exploring the etiology of YEL-AVD.

Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays.

Background Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. Methods We collected paired NP and OP swabs separately from pediatric and adult patients with influenza-like illness or severe acute respiratory illness at two respiratory surveillance sites in Kenya. The specimens were tested for eight respiratory viruses by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Positivity for a specific virus was defined as detection of viral nucleic acid in either swab. Results Of 2,331 paired NP/OP specimens, 1,402 (60.1%) were positive for at least one virus, and 393 (16.9%) were positive for more than one virus. Overall, OP swabs were significantly more sensitive than NP swabs for adenovirus (72.4% vs. 57.6%, p<0.01) and 2009 pandemic influenza A (H1N1) virus (91.2% vs. 70.4%, p<0.01). NP specimens were more sensitive for influenza B virus (83.3% vs. 61.5%, p = 0.02), parainfluenza virus 2 (85.7%, vs. 39.3%, p<0.01), and parainfluenza virus 3 (83.9% vs. 67.4%, p<0.01). The two methods did not differ significantly for human metapneumovirus, influenza A (H3N2) virus, parainfluenza virus 1, or respiratory syncytial virus. Conclusions The sensitivities were variable among the eight viruses tested; neither specimen was consistently more effective than the other. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach.

Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010

BackgroundRefugees are at risk for poor outcomes from acute respiratory infections (ARI) because of overcrowding, suboptimal living conditions, and malnutrition. We implemented surveillance for respiratory viruses in Dadaab and Kakuma refugee camps in Kenya to characterize their role in the epidemiology of ARI among refugees.MethodsFrom 1 September 2007 through 31 August 2010, we obtained nasopharyngeal (NP) and oropharyngeal (OP) specimens from patients with influenza-like illness (ILI) or severe acute respiratory infections (SARI) and tested them by RT-PCR for adenovirus (AdV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza viruses (PIV), and influenza A and B viruses. Definitions for ILI and SARI were adapted from those of the World Health Organization. Proportions of cases associated with viral aetiology were calculated by camp and by clinical case definition. In addition, for children < 5 years only, crude estimates of rates due to SARI per 1000 were obtained.ResultsWe tested specimens from 1815 ILI and 4449 SARI patients (median age = 1 year). Proportion positive for virus were AdV, 21.7%; RSV, 12.5%; hMPV, 5.7%; PIV, 9.4%; influenza A, 9.7%; and influenza B, 2.6%; 49.8% were positive for at least one virus. The annual rate of SARI hospitalisation for 2007-2010 was 57 per 1000 children per year. Virus-positive hospitalisation rates were 14 for AdV; 9 for RSV; 6 for PIV; 4 for hMPV; 5 for influenza A; and 1 for influenza B. The rate of SARI hospitalisation was highest in children < 1 year old (156 per 1000 child-years). The ratio of rates for children < 1 year and 1 to < 5 years old was 3.7:1 for AdV, 5.5:1 for RSV, 4.4:1 for PIV, 5.1:1 for hMPV, 3.2:1 for influenza A, and 2.2:1 for influenza B. While SARI hospitalisation rates peaked from November to February in Dadaab, no distinct seasonality was observed in Kakuma.ConclusionsRespiratory viral infections, particularly RSV and AdV, were associated with high rates of illness and make up a substantial portion of respiratory infection in these two refugee settings.

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

We evaluated whether coadministration of the yellow fever (YF) virus vaccine with human immunoglobulin (Ig) that contained YF virus-neutralizing antibodies would reduce post-vaccination viremia without compromising immunogenicity and thus, potentially mitigate YF vaccine-associated adverse events. We randomized 80 participants to receive either YF vaccine and Ig or YF vaccine and saline placebo. Participants were followed for 91 days for safety and assessments of viremia and immunogenicity. There were no differences found between the two groups in the proportion of vaccinated participants who developed viremia, seroconversion, cluster of differentiation (CD)-8(+) and CD4(+) T-cell responses, and cytokine responses. These results argue against one putative explanation for the increased reporting of YF vaccine side effects in recent years (i.e., a change in travel clinic practice after 1996 when hepatitis A prophylaxis with vaccine replaced routine use of pre-travel Ig, thus potentially removing an incidental YF vaccine-attenuating effect of anti-YF virus antibodies present in Ig).

Risk Factors for Measles Mortality Among Hospitalized Somali Refugees Displaced by Famine, Kenya, 2011

BACKGROUND Measles among displaced, malnourished populations can result in a high case fatality ratio. In 2011, a large measles outbreak occurred in Dadaab, Kenya, among refugees fleeing famine and conflict in Somalia. The aim of this study was to identify predictors of measles deaths among hospitalized patients during the outbreak. METHODS A retrospective cohort study design was used to investigate measles mortality among hospitalized measles patients with a date of rash onset during 6 June-10 September 2011. Data were abstracted from medical records and a measles case was defined as an illness with fever, maculopapular rash, and either cough, coryza or conjunctivitis. Vaccination status was determined by patient or parental recall. Independent predictors of mortality were identified using logistic regression analysis. RESULTS Of 388 hospitalized measles patients, 188 (49%) were from hospital X, 70 (18%) from hospital Y, and 130 (34%) from hospital Z; median age was 22 years, 192 (50%) were 15-29 years of age, and 22 (6%) were vaccinated. The mean number of days from rash onset to hospitalization varied by hospital (hospital X = 5, hospital Y = 3, hospital Z = 6; P < .0001). Independent risk factors for measles mortality were neurological complications (odds ratio [OR], 12.8; 95% confidence interval [CI], 3.1-52.4), acute malnutrition (OR, 7.6; 95% CI, 1.3-44.3), and admission to hospital Z (OR, 4.2; 95% CI, 1.3-13.2). CONCLUSIONS Among Somali refugees, in addition to timely vaccination at border crossing points, early detection and treatment of acute malnutrition and proper management of measles cases may reduce measles mortality.

Examining strain diversity and phylogeography in relation to an unusual epidemic pattern of respiratory syncytial virus (RSV) in a long-term refugee camp in Kenya

BackgroundA recent longitudinal study in the Dadaab refugee camp near the Kenya-Somalia border identified unusual biannual respiratory syncytial virus (RSV) epidemics. We characterized the genetic variability of the associated RSV strains to determine if viral diversity contributed to this unusual epidemic pattern.MethodsFor 336 RSV positive specimens identified from 2007 through 2011 through facility-based surveillance of respiratory illnesses in the camp, 324 (96.4%) were sub-typed by PCR methods, into 201 (62.0%) group A, 118 (36.4%) group B and 5 (1.5%) group A-B co-infections. Partial sequencing of the G gene (coding for the attachment protein) was completed for 290 (89.5%) specimens. These specimens were phylogenetically analyzed together with 1154 contemporaneous strains from 22 countries.ResultsOf the 6 epidemic peaks recorded in the camp over the period, the first and last were predominantly made up of group B strains, while the 4 in between were largely composed of group A strains in a consecutive series of minor followed by major epidemics. The Dadaab group A strains belonged to either genotype GA2 (180, 98.9%) or GA5 (2, < 1%) while all group B strains (108, 100%) belonged to BA genotype. In sequential epidemics, strains within these genotypes appeared to be of two types: those continuing from the preceding epidemics and those newly introduced. Genotype diversity was similar in minor and major epidemics.ConclusionRSV strain diversity in Dadaab was similar to contemporaneous diversity worldwide, suggested both between-epidemic persistence and new introductions, and was unrelated to the unusual epidemic pattern.

Cholera Mortality during Urban Epidemic, Dar es Salaam, Tanzania, August 16, 2015–January 16, 20161

In 2015, a cholera epidemic occurred in Tanzania; most cases and deaths occurred in Dar es Salaam early in the outbreak. We evaluated cholera mortality through passive surveillance, burial permits, and interviews conducted with decedents’ caretakers. Active case finding identified 101 suspected cholera deaths. Routine surveillance had captured only 48 (48%) of all cholera deaths, and burial permit assessments captured the remainder. We interviewed caregivers of 56 decedents to assess cholera management behaviors. Of 51 decedents receiving home care, 5 (10%) used oral rehydration solution after becoming ill. Caregivers reported that 51 (93%) of 55 decedents with known time of death sought care before death; 16 (29%) of 55 delayed seeking care for >6 h. Of the 33 (59%) community decedents, 20 (61%) were said to have been discharged from a health facility before death. Appropriate and early management of cholera cases can reduce the number of cholera deaths.

Health care utilization for acute illnesses in an urban setting with a refugee population in Nairobi, Kenya: a cross-sectional survey

BackgroundEstimates place the number of refugees in Nairobi over 100,000. The constant movement of refugees between countries of origin, refugee camps, and Nairobi poses risk of introduction and transmission of communicable diseases into Kenya. We assessed the care-seeking behavior of residents of Eastleigh, a neighborhood in Nairobi with urban refugees.MethodsDuring July and August 2010, we conducted a Health Utilization Survey in Section II of Eastleigh. We used a multistage random cluster sampling design to identify households for interview. A standard questionnaire on the household demographics, water and sanitation was administered to household caretakers. Separate questionnaires were administered to household members who had one or more of the illnesses of interest.ResultsOf 785 households targeted for interview, data were obtained from 673 (85.7%) households with 3,005 residents. Of the surveyed respondents, 290 (9.7%) individuals reported acute respiratory illness (ARI) in the previous 12 months, 222 (7.4%) reported fever in the preceding 2 weeks, and 54 (1.8%) reported having diarrhea in the 30 days prior to the survey. Children <5 years old had the highest frequency of all the illnesses surveyed: 17.1% (95% CI 12.2-21.9) reported ARI, 10.0% (95% CI 6.2-13.8) reported fever, and 6.9% (3.8-10.0) reported diarrhea during the time periods specified for each syndrome. Twenty-nine [7.5% (95% CI 4.3-10.7)] hospitalizations were reported among all age groups of those who sought care. Among participants who reported ≥1 illness, 330 (77.0%) sought some form of health care; most (174 [59.8%]) sought health care services from private health care providers. Fifty-five (18.9%) participants seeking healthcare services visited a pharmacy. Few residents of Eastleigh (38 [13.1%]) sought care at government-run facilities, and 24 (8.2%) sought care from a relative, a religious leader, or a health volunteer. Of those who did not seek any health care services (99 [23.0%]), the primary reason was cost (44.8%), followed by belief that the person was not sick enough (34.6%).ConclusionHealth care utilization in Eastleigh is high; however, a large proportion of residents opt to seek care at private clinics or pharmacies, despite the availability of accessible government-provided health care services in this area.

Developing a multisectoral National Action Plan for Health Security (NAPHS) to implement the International Health Regulations (IHR 2005) in Tanzania

The Ebola outbreak in West Africa precipitated a renewed momentum to ensure global health security through the expedited and full implementation of the International Health Regulations (IHR) (2005) in all WHO member states. The updated IHR (2005) Monitoring and Evaluation Framework was shared with Member States in 2015 with one mandatory component, that is, States Parties annual reporting to the World Health Assembly (WHA) on compliance and three voluntary components: Joint External Evaluation (JEE), After Action Reviews and Simulation Exercises. In February 2016, Tanzania, was the first country globally to volunteer to do a JEE and the first to use the recommendations for priority actions from the JEE to develop a National Action Plan for Health Security (NAPHS) by February 2017. The JEE demonstrated that within the majority of the 47 indicators within the 19 technical areas, Tanzania had either ‘limited capacity’ or ‘developed capacity’. None had ‘sustainable capacity’. With JEE recommendations for priority actions, recommendations from other relevant assessments and complementary objectives, Tanzania developed the NAPHS through a nationwide consultative and participatory process. The 5-year cost estimate came out to approximately US