The First Outbreak of Autochthonous Zika Virus in Sabah, Malaysian Borneo

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Background: Zika virus (ZIKV) infection is a public health concern. The first ZIKV outside Africa was detected in mosquito in Malaysia. More than six decades ago, serological surveys indicated the presence of human infection with ZIKV in the Malaysian Borneo state of Sabah. It has also been demonstrated that orangutans in Sabah have antibodies against ZIKV. Several years ago, a case of human ZIKV infection was reported in a traveler who visited Sabah. Therefore, it is thought that ZIKV is endogenous to Sabah and is widely distributed.  During the recent global epidemic of ZIKV, the first autochthonous case and two subsequent autochthonous cases were detected in Sabah. Because ZIKV infection is mainly asymptomatic or mildly symptomatic, the extent of ZIKV infection in the population of Sabah is not known. Furthermore, the presence of ZIKV in vector mosquitoes and animals has not been investigated. Therefore, the present study was performed to analyze the outbreak cases of ZIKV infection and to determine their relationship with the burden of ZIKV infection in the local population, mosquitoes, and wild nonhuman primates in Sabah. 

Methods: Serum and urine samples were collected from two local patients with ZIKV infection, their household members, and those who resided within 400m of the patients’ residences. Serum samples were also collected from four wild Maca fascicularis. Mosquito samples, mostly female Aedes albopictus, were collected from 30 sites in Kota Kinabalu. The presence of ZIKV was assessed by RT-qPCR and RT-PCR. Phylogenetic analysis was performed using the neighbor-joining method.  

Results: Two cases of ZIKV infection were identified by reverse-transcription quantitative PCR (RT-qPCR) in residents of Kota Kinabalu, and the Taiwanese health authorities reported one case in an individual who visited Kota Kinabalu during the study period. All household members of both local patients and people living within a 400 m radius of the patients were negative for ZIKV. Furthermore, mosquitoes collected from the surroundings of the residences and places visited by the patients and four serum samples from M. fascicularis were also negative for ZIKV. A phylogenetic tree constructed using the nucleotide sequences of the envelope genes of ZIKV showed that the strains from Sabah formed a cluster with strains from Thailand and Cambodia, and belong to the Asian lineage. 

Conclusions: Our study revealed that ZIKVs in Sabah is of Asian lineage and are not related to the recent outbreak strains in the Americas and Singapore. ZIKV infection in Sabah is sporadic, possibly because of limited transmission of the virus. Further studies are needed to characterize the evolutionary history of ZIKV in Sabah to understand the epidemiology of this infection in Borneo.

A Nosocomial Outbreak of Clinical Sepsis in a Neonatal Care Unit (NCU) in Port-Au-Prince Haiti, July 2014 – September 2015.

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Introduction

Between July 2014 and September 2015, a neonatal care unit (NCU) in Port Au Prince, Haiti, experienced an outbreak of sepsis, most probably due to nosocomial transmission of Extended Beta Lactamase (ESBL) producing gram negative bacteria, included Klebsiella pneumoniae.

Methods

We describe the epidemiological and microbiological activities performed as part of the outbreak investigation and the control measures implemented throughout this period.

Results

During the study period 257 cases of sepsis were reported, of which 191 died. The case fatality decreased from 100% in July 2014 to 24% in September 2015 and could be attributed to an improvement in clinical management and strengthened infection prevention and control measures. Risk factors identified to be associated with having late onset sepsis (sepsis onset >48 hours after birth)(n=205/257, 79. included: all categories of birthweight lower than <2500g (p=<0.0001) and all categories of gestational age younger than 36 weeks (p=0.0002). Microbiological investigations confirmed that out of 32 isolates (N=55; 58%) that were positive for gram negative bacteria, 27 (89%) were due to K. pneumoniae and most of these were from single MLST type (ST37).

Discussion 

This outbreak highlighted the importance of epidemiological and microbiological surveillance during an outbreak of sepsis in a NCU in a low resource setting, including regular point prevalence surveys.

Invasive Meningococcal Meningitis Serogroup C Outbreak in Northwest Nigeria, 2015 – Third Consecutive Outbreak of a New Strain

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BACKGROUND: In northwest Nigeria in 2013 and 2014, two sequential, localized outbreaks of meningitis were caused by a new strain of Neisseria meningitidis serogroup C (NmC). In 2015, an outbreak caused by the same novel NmC strain occurred over a wider geographical area, displaying different characteristics to the previous outbreaks. We describe cases treated by Médecins Sans Frontières (MSF) in the 2015 outbreak. 

METHODS: From February 10 to June 8, 2015, data on cerebrospinal meningitis (CSM) cases and deaths were recorded on standardized line-lists from case management sites supported by MSF. Cerebrospinal fluid (CSF) samples from suspected cases at the beginning of the outbreak and throughout from suspected cases from new geographical areas were tested using rapid Pastorex® latex agglutination to determine causative serogroup. A subset of CSF samples was also inoculated into Trans-Isolate medium for testing by the WHO Collaborating Centre for Reference and Research on Meningococci, Oslo. Reactive vaccination campaigns with meningococcal ACWY polysaccharide vaccine targeted affected administrative wards. 

RESULTS: A total of 6394 (65 confirmed and 6329 probable) cases of CSM including 321 deaths (case fatality rate: 5.0%) were recorded. The cumulative attack rate was 282 cases per 100,000 population in the wards affected. The outbreak lasted 17 weeks, affecting 1039 villages in 21 local government areas in three states (Kebbi, Sokoto, Niger). Pastorex® tests were NmC positive for 65 (58%) of 113 CSF samples. Of 31 Trans-Isolate medium samples, 26 (84%) tested positive for NmC (14 through culture and 12 through PCR); all had the same rare PorA type P1.21-15,16 as isolates from the 2013 and 2014 outbreaks. All 14 culture-positive samples yielded isolates of the same genotype (ST-10217 PorA type P1.21-15,16 and FetA type F1-7). More than 222,000 targeted individuals were vaccinated relatively early in the outbreak (administrative coverage estimates 98% and 89% in Kebbi and Sokoto, respectively). 

CONCLUSIONS: The outbreak was the largest caused by NmC documented in Nigeria. Reactive vaccination in both states may have helped curtail the epidemic. A vaccination campaign against NmC with a long-lasting conjugate vaccine should be considered in the region.

Zika Virus, Elevation, and Transmission Risk

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Introduction: Zika virus has appeared in the Americas in the form of a major outbreak, and is now known to cause birth defects when pregnant women are infected. As a result, the Centers for Disease Control and Prevention issued travel guidelines, in the form of an elevational risk definition: destinations below 2000m are considered as at-risk.

Methods: We explored the distribution of known Zika virus vector mosquito species in relation to climatic conditions, elevation, latitude, and air traffic connections to the United States.

Results: In view of the tropical and subtropical nature of the mosquito species that are the primary Zika virus vectors, we point out that climate varies rather dramatically with respect to elevation and latitude, such that a single elevational criterion will be a poor predictor of potential for transmission.

Discussion: We suggest an initial adjustment would consider latitude in addition to elevation; a more definitive, quantitative analysis of risk would consider variables of ecology, climate, human condition, and connectivity of areas.

Epidemiology of Chikungunya Virus in Bahia, Brazil, 2014-2015

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Chikungunya is an emerging arbovirus that is characterized into four lineages. One of these, the Asian genotype, has spread rapidly in the Americas after its introduction in the Saint Martin island in October 2013. Unexpectedly, a new lineage, the East-Central-South African genotype, was introduced from Angola in the end of May 2014 in Feira de Santana (FSA), the second largest city in Bahia state, Brazil, where over 5,500 cases have now been reported. Number weekly cases of clinically confirmed CHIKV in FSA were analysed alongside with urban district of residence of CHIKV cases reported between June 2014 and October collected from the municipality’s surveillance network. The number of cases per week from June 2014 until September 2015 reveals two distinct transmission waves. The first wave ignited in June and transmission ceased by December 2014. However, a second transmission wave started in January and peaked in May 2015, 8 months after the first wave peak, and this time in phase with Dengue virus and Zika virus transmission, which ceased when minimum temperature dropped to approximately 15°C. We find that shorter travelling times from the district where the outbreak first emerged to other urban districts of FSA were strongly associated with incidence in each district in 2014 (R2).

Whole Genome Sequence Analysis of Salmonella Enteritidis PT4 Outbreaks from a National Reference Laboratory’s Viewpoint

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Introduction: In April and May 2014, two suspected egg-related outbreaks of Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) were investigated by the Belgian National Reference Laboratory of Foodborne Outbreaks. Both the suspected food and human isolates being available, and this for both outbreaks, made these the ideal case study for a retrospective whole genome sequencing (WGS) analysis with the goal to investigate the feasibility of this technology for outbreak investigation by a National Reference Laboratory or National Reference Centre without thorough bioinformatics expertise.

Methods: The two outbreaks were originally investigated epidemiologically with a standard questionnaire and with serotyping, phage typing, multiple-locus variable-number of tandem repeats analysis (MLVA) and antimicrobial susceptibility testing as classical microbiological methods. Retrospectively, WGS of six outbreak isolates was done on an Illumina HiSeq. Analysis of the WGS data was performed with currently available, user-friendly software and tools, namely CLC Genomics Workbench, the tools available on the server of the Center for Genomic Epidemiology and BLAST Ring Image Generator (BRIG).

Results: To all collected human and food outbreak isolates, classical microbiological investigation assigned phage type PT4 (variant phage type PT4a for one human isolate) and MLVA profile 3-10-5-4-1, both of which are common for human isolates in Belgium. The WGS analysis confirmed the link between food and human isolates for each of the outbreaks and clearly discriminated between the two outbreaks occurring in a same time period, thereby suggesting a non-common source of contamination. Also, an additional plasmid carrying an antibiotic resistance gene was discovered in the human isolate with the variant phage type PT4a.

Discussion: For the two investigated outbreaks occurring at geographically separated locations, the gold standard classical microbiological subtyping methods were not sufficiently discriminative to distinguish between or assign a common origin of contamination for the two outbreaks, while WGS analysis could do so. This case study demonstrated the added value of WGS for outbreak investigations by confirming and/or discriminating food and human isolates between and within outbreaks. It also proved the feasibility of WGS as complementary or even future replacing (sub)typing method for the average routine laboratory.

Sequential Outbreaks Due to a New Strain of Neisseria Meningitidis Serogroup C in Northern Nigeria, 2013-14

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Background
Neisseria meningitidis serogroup C (NmC) outbreaks occur infrequently in the African meningitis belt; the most recent report of an outbreak of this serogroup was in Burkina Faso, 1979. Médecins sans Frontières (MSF) has been responding to outbreaks of meningitis in northwest Nigeria since 2007 with no reported cases of serogroup C from 2007-2012. MenAfrivac®, a serogroup A conjugate vaccine, was first used for mass vaccination in northwest Nigeria in late 2012. Reactive vaccination using polysaccharide ACYW135 vaccine was done by MSF in parts of the region in 2008 and 2009; no other vaccination campaigns are known to have occurred in the area during this period. We describe the general characteristics of an outbreak due to a novel strain of NmC in Sokoto State, Nigeria, in 2013, and a smaller outbreak in 2014 in the adjacent state, Kebbi.

Methods
Information on cases and deaths was collected using a standard line-list during each week of each meningitis outbreak in 2013 and 2014 in northwest Nigeria. Initial serogroup confirmation was by rapid Pastorex agglutination tests. Cerebrospinal fluid (CSF) samples from suspected meningitis patients were sent to the WHO Reference Laboratory in Oslo, where bacterial isolates, serogrouping, antimicrobial sensitivity testing, genotype characterisation and real-time PCR analysis were performed.

Results
In the most highly affected outbreak areas, all of the 856 and 333 clinically suspected meningitis cases were treated in 2013 and 2014, respectively. Overall attack (AR) and case fatality (CFR) rates were 673/100,000 population and 6.8% in 2013, and 165/100,000 and 10.5% in 2014. Both outbreaks affected small geographical areas of less than 150km2 and populations of less than 210,000, and occurred in neighbouring regions in two adjacent states in the successive years. Initial rapid testing identified NmC as the causative agent. Of the 21 and 17 CSF samples analysed in Oslo, NmC alone was confirmed in 11 and 10 samples in 2013 and 2014, respectively. Samples confirmed as NmC through bacterial culture had sequence type (ST)-10217.

Conclusions
These are the first recorded outbreaks of NmC in the region since 1979, and the sequence (ST)-10217 has not been identified anywhere else in the world. The outbreaks had similar characteristics to previously recorded NmC outbreaks. Outbreaks of NmC in 2 consecutive years in northern Nigeria indicate a possible emergence of this serogroup. Increased surveillance for multiple serogroups in the region is needed, along with consideration of vaccination with conjugate vaccines rather than for NmA alone.

A Three-Scale Network Model for the Early Growth Dynamics of 2014 West Africa Ebola Epidemic

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Background: In mid-October 2014, the number of cases of the West Africa Ebola virus epidemic in Guinea, Sierra Leone and Liberia exceeded 9,000 cases. The early growth dynamics of the epidemic has been qualitatively different for each of the three countries. However, it is important to understand these disparate dynamics as trends of a single epidemic spread over regions with similar geographic and cultural aspects, with likely common parameters for transmission rates and reproduction number R0.

Methods: We combine a discrete, stochastic SEIR model with a three-scale community network model to demonstrate that the different regional trends may be explained by different community mixing rates. Heuristically, the effect of different community mixing rates may be understood as the observation that two individuals infected by the same chain of transmission are more likely to share the same contacts in a less-mixed community. Local saturation effects occur as the contacts of an infected individual are more likely to already be exposed by the same chain of transmission.

Results: The effects of community mixing, together with stochastic effects, can explain the qualitative difference in the growth of Ebola virus cases in each country, and why the probability of large outbreaks may have recently increased. An increase in the rate of Ebola cases in Guinea in late August, and a local fitting of the transient dynamics of the Ebola cases in Liberia, suggests that the epidemic in Liberia has been more severe, and the epidemic in Guinea is worsening, due to discrete seeding events as the epidemic spreads into new communities.

Conclusions: A relatively simple network model provides insight on the role of local effects such as saturation that would be difficult to otherwise quantify. Our results predict that exponential growth of an epidemic is driven by the exposure of new communities, underscoring the importance of limiting this spread.

Conservancy of mAb Epitopes in Ebolavirus Glycoproteins of Previous and 2014 Outbreaks

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Background: Several monoclonal antibodies (mAb) are being evaluated as treatment options for the current 2014 Ebola outbreak. But they were derived from and tested for protection against the older 1976 Mayinga or 1995 Kikwit Zaire Ebolaviruses (EBOV). The EBOV sequences reported for the current outbreak contain several mutations whose significance remained to be established.

Methods: We analyzed sequence and structural conservation of the Ebolavirus glycoprotein (GP) epitopes for all experimentally identified protective mAbs published to date.

Results: The conservancy analysis of protective mAb epitopes in the Ebolavirus glycoprotein sequences spanning all Ebola virus lineages since 1976 showed that conservancy within the Zaire EBOV lineage was high, with only one immunodominant epitope of mAb 13F6-1-2 acquiring two novel mutations in the 2014 outbreak that might potentially change the antibody specificity and neutralization activity. However, the conservation to other Ebola viruses was unexpectedly low.

Conclusion: Low conservancy of Zaire EBOV mAb epitopes to other EBOV lineages suggests that these epitopes are not indispensable for viral fitness, and that alternative mAbs could be developed to broadly target all EBOV. However, average percent sequence identity of the epitopes for mAbs used in current cocktails to the Zaire EBOV is high with only one epitope differing in the 2014 outbreak. These data bode well for general usefulness of these antibodies in the context of the current outbreak.

Commentary: Containing the Ebola Outbreak – the Potential and Challenge of Mobile Network Data

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Commentary The ongoing Ebola outbreak is taking place in one of the most highly connected and densely populated regions of Africa (Figure 1A). Accurate information on population movements is valuable for monitoring the progression of the outbreak and predicting its future spread, facilitating the prioritization of interventions and designing surveillance and containment strategies. Vital questions […]

Assessing the International Spreading Risk Associated with the 2014 West African Ebola Outbreak

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Background: The 2014 West African Ebola Outbreak is so far the largest and deadliest recorded in history. The affected countries, Sierra Leone, Guinea, Liberia, and Nigeria, have been struggling to contain and to mitigate the outbreak. The ongoing rise in confirmed and suspected cases, 2615 as of 20 August 2014, is considered to increase the risk of international dissemination, especially because the epidemic is now affecting cities with major commercial airports.

Method: We use the Global Epidemic and Mobility Model to generate stochastic, individual based simulations of epidemic spread worldwide, yielding, among other measures, the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. The mobility model integrates daily airline passenger traffic worldwide and the disease model includes the community, hospital, and burial transmission dynamic. We use a multimodel inference approach calibrated on data from 6 July to the date of 9 August 2014. The estimates obtained were used to generate a 3-month ensemble forecast that provides quantitative estimates of the local transmission of Ebola virus disease in West Africa and the probability of international spread if the containment measures are not successful at curtailing the outbreak.

Results: We model the short-term growth rate of the disease in the affected West African countries and estimate the basic reproductive number to be in the range 1.5 − 2.0 (interval at the 1/10 relative likelihood). We simulated the international spreading of the outbreak and provide the estimate for the probability of Ebola virus disease case importation in countries across the world. Results indicate that the short-term (3 and 6 weeks) probability of international spread outside the African region is small, but not negligible. The extension of the outbreak is more likely occurring in African countries, increasing the risk of international dissemination on a longer time scale.

Phylogenetic Analysis of Guinea 2014 EBOV Ebolavirus Outbreak

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Members of the genus Ebolavirus have caused outbreaks of haemorrhagic fever in humans in Africa. The most recent outbreak in Guinea, which began in February of 2014, is still ongoing. Recently published analyses of sequences from this outbreak suggest that the outbreak in Guinea is caused by a divergent lineage of Zaire ebolavirus. We report evidence that points to the same Zaire ebolavirus lineage that has previously caused outbreaks in the Democratic Republic of Congo, the Republic of Congo and Gabon as the culprit behind the outbreak in Guinea.

West Nile Virus Transmission in Winter: The 2013 Great Salt Lake Bald Eagle and Eared Grebes Mortality Event

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West Nile Virus (WNV) infection has been reported in over 300 species of birds and mammals. Raptors such as eagles, hawks and falcons are remarkably susceptible, but reports of WNV infection in Bald Eagles (Haliaeetus leucocephalus) are rare and reports of WNV infection in grebes (Podicipediformes) even rarer. We report an unusually large wild bird mortality event involving between 15,000-20,000 Eared Grebes (Podiceps nigricollis) and over 40 Bald Eagles around the Great Salt Lake, Utah, in November-December 2013. Mortality in grebes was first reported in early November during a period when the area was unseasonably warm and the grebes were beginning to gather and stage prior to migration. Ten out of ten Eared Grebes collected during this period were WNV RT-PCR and/or isolation positive. This is the first report of WNV infection in Eared Grebes and the associated mortality event is matched in scale only by the combined outbreaks in American White Pelican (Pelecanus erythrorhynchos) colonies in the north central states in 2002-2003. We cannot be sure that all of the grebes were infected by mosquito transmission; some may have become infected through contact with WNV shed orally or cloacally from other infected grebes. Beginning in early December, Bald Eagles in the Great Salt Lake area were observed to display neurological signs such as body tremors, limb paralysis and lethargy. At least 43 Bald Eagles had died by the end of the month. Nine of nine Bald Eagles examined were infected with WNV. To the best of our knowledge, this is the largest single raptor mortality event since WNV became endemic in the USA. Because the majority of the eagles affected were found after onset of below-freezing temperatures, we suggest at least some of the Bald Eagles were infected with WNV via consumption of infected Eared Grebes or horizontal transmission at roost sites.