Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Ntshoe, Genevie; McAnerney, Johanna M.; Archer, Brett N.; Smit, Sheilagh B.; Harris, Bernice Nerine; Tempia, Stefano; Mashele, Mirriam; Singh, Beverley; Thomas, Juno; Cengimbo, Ayanda; Blumberg, Lucille; Puren, Adrian; Moyes, Jocelyn; Heever, Johann Van den; Schoub, Barry D.; Cohen, Cheryl

doi:10.1371/journal.pone.0055682

Cited by 42 publications

(43 citation statements)

References 11 publications

(14 reference statements)

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“…I n 2009-2010, a single measles virus (MeV) strain (genotype B3) was responsible for an extensive measles outbreak in South Africa (1). During this epidemic, numerous HIV-infected patients were diagnosed with measles inclusion body encephalitis (MIBE) (2), constituting the largest MIBE case series ever reported.…”

Section: Abstract Central Nervous System Infections Measles Viral Fmentioning

confidence: 99%

Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

Angius

Smuts

Rybkina

et al. 2019

J Virol

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During a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain. IMPORTANCE Measles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.

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Section: Abstract Central Nervous System Infections Measles Viral Fmentioning

confidence: 99%

Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

Angius

Smuts

Rybkina

et al. 2019

J Virol

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“…Sequences that were identical or closely related to the sequences of the named strain, MVi/Harare.ZWE/38.09, were found in all provinces where samples were collected throughout the study period, indicating that this strain was endemic in the Democratic Republic of the Congo in 2014. Genotype B3 has been the predominant genotype in sub-Saharan Africa since the outbreaks in South Africa in 2009 (45,46). Genotype B3 sequences closely related to MVi/Harare.ZWE/38.09 have been identified in many countries worldwide (47)(48)(49)(50), following the 2013 to 2014 outbreak in the Philippines (51).…”

Section: Discussionmentioning

confidence: 99%

Use of FTA Cards To Transport Throat Swabs and Oral Fluid Samples for Molecular Detection and Genotyping of Measles and Rubella Viruses

et al. 2019

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The genetic characterization of measles viruses is an important tool for measles surveillance. Reverse cold chain requirements for the transportation of samples to reference laboratories are challenging in resource-limited settings. FTA cards facilitate the transport of virologic samples at ambient temperature as noninfectious material; however, the utility of FTA cards for the detection and genotyping of measles virus from clinical samples has not been evaluated. Throat swabs (TS) and oral fluid (OF) samples were collected from suspected measles cases in the Democratic Republic of the Congo. Virus detection (reverse transcription-quantitative real-time PCR [RT-qPCR]) and genotyping (endpoint RT-PCR) were compared for samples from 238 suspected cases; these samples were either transported using the reverse cold chain or at ambient temperature on FTA cards. Virus detection showed excellent positive agreement for OF samples compared to TS (95.3%; confidence interval [CI], 91.6 to 97.4), in contrast to 79.4% (CI, 73.5 to 84.3) for TS on FTA, and 85.5% (CI, 80.2 to 89.6) for OF on FTA compared to OF samples. Genotyping results obtained for a subset of samples indicated that 77.3% of all TS and 71.0% of OF samples would produce genotype information compared to 41.6% of TS and 41.3% of OF on FTA cards. Similar results were found for 16 measles-negative samples that were confirmed as rubella cases. Measles genotype B3 and rubella genotype 2B were detected. FTA cards have limited utility for virologic surveillance of sporadic cases of measles; however, they can be a useful tool for the expansion of virologic surveillance in countries where the reverse cold chain is not available.

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“…The NDSS perceptions of key stakeholders in this study differed from the experience of the successful containment of several high profile outbreaks in South Africa since 2008, which included a novel arenavirus, Lujovirus [28]; a major cholera outbreak [29, 30]; influenza pandemic [31]; a Rift Valley Fever outbreak [32]; and a measles outbreak [33]. However, the high media attention during these events could have increased the index of suspicion and sensitivity of the surveillance system, which might not be a true reflection of the South African NDSS.…”

Section: Discussionmentioning

confidence: 99%

Survey of the perceptions of key stakeholders on the attributes of the South African Notifiable Diseases Surveillance System

Benson

Musekiwa²,

Blumberg

et al. 2016

BMC Public Health

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BackgroundAn effective and efficient notifiable diseases surveillance system (NDSS) is essential for a rapid response to disease outbreaks, and the identification of priority diseases that may cause national, regional or public health emergencies of international concern (PHEICs). Regular assessments of country-based surveillance system are needed to enable countries to respond to outbreaks before they become PHEICs. As part of a broader evaluation of the NDSS in South Africa, the aim of the study was to determine the perceptions of key stakeholders on the national NDSS attributes of acceptability, flexibility, simplicity, timeliness and usefulness.MethodsDuring 2015, we conducted a nationally representative cross-sectional survey of communicable diseases coordinators and surveillance officers, as well as members of NDSS committees. Individuals with less than 1 year experience of the NDSS were excluded. Consenting participants completed a self-administered questionnaire. The questionnaire elicited information on demographic information and perceptions of the NDSS attributes. Data were analysed using descriptive statistics and the unconditional logistic regression model.ResultsMost stakeholders interviewed (53 %, 60/114) were involved in disease control and response. The median number of years of experience with the NDSS was 11 years (inter-quartile range (IQR): 5 to 20 years). Regarding the NDSS attributes, 25 % of the stakeholders perceived the system to be acceptable, 51 % to be flexible, 45 % to be timely, 61 % to be useful, and 74 % to be simple. Health management stakeholders perceived the system to be more useful and timely compared to the other stakeholders. Those with more years of experience were less likely to perceive the NDSS system as acceptable (OR 0.91, 95 % CI: 0.84–1.00, p = 0.041); those in disease detection were less likely to perceive it as timely (OR 0.10, 95 % CI: 0.01–0.96, p = 0.046) and those participating in National Outbreak Response Team were less likely to perceive it as useful (OR 0.38, 95 % CI: 0.16–0.93, p = 0.034).ConclusionThe overall poor perceptions of key stakeholder on the system attributes are a cause for concern. The study findings should inform the revitalisation and reform of the NDSS in South Africa, done in consultation and partnership with the key stakeholders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3781-7) contains supplementary material, which is available to authorized users.

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Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Cited by 42 publications

References 11 publications

Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

Use of FTA Cards To Transport Throat Swabs and Oral Fluid Samples for Molecular Detection and Genotyping of Measles and Rubella Viruses

Survey of the perceptions of key stakeholders on the attributes of the South African Notifiable Diseases Surveillance System

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