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1.  Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011 
PLoS ONE  2013;8(2):e55682.
Background
Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa.
Methods
Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa.
Results
A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented.
Conclusion
We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.
doi:10.1371/journal.pone.0055682
PMCID: PMC3577838  PMID: 23437059
2.  Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa 
PLoS ONE  2012;7(11):e49482.
Background/Objective
Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial Rt) and the temporal variation of Rt.
Methods
We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1) for simultaneous estimation of initial Rt and the SI; estimate initial Rt from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of Rt.
Results
12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean Rt of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1). Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial Rt of 1.43 (95% CI: 1.38–1.49) (method 2). The mean Rt peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and Rt>1 was sustained until August 22 (method 3).
Conclusions
Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings.
doi:10.1371/journal.pone.0049482
PMCID: PMC3500305  PMID: 23166682
3.  Trimethoprim-Sulfamethoxazole Prophylaxis and Antibiotic Nonsusceptibility in Invasive Pneumococcal Disease 
Among 5,043 invasive pneumococcal disease (IPD) isolates identified through South African national surveillance from 2003 to 2007, we estimated the effect of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis on antimicrobial resistance. Patients on TMP-SMX prophylaxis were more likely to have a pneumococcal isolate nonsusceptible to TMP-SMX, penicillin, and rifampin. TMP-SMX nonsusceptibility was associated with nonsusceptibility to penicillin, erythromycin, and rifampin and multidrug resistance. This study informs empirical treatment of suspected IPD in patients with a history of TMP-SMX use.
doi:10.1128/AAC.05813-11
PMCID: PMC3294938  PMID: 22232291
4.  Elevated Influenza-Related Excess Mortality in South African Elderly Individuals, 1998–2005 
Background. Although essential to guide control measures, published estimates of influenza-related seasonal mortality for low- and middle-income countries are few. We aimed to compare influenza-related mortality among individuals aged ⩾65 years in South Africa and the United States.
Methods. We estimated influenza-related excess mortality due to all causes, pneumonia and influenza, and other influenza-associated diagnoses from monthly age-specific mortality data for 1998–2005 using a Serfling regression model. We controlled for between-country differences in population age structure and nondemographic factors (baseline mortality and coding practices) by generating age-standardized estimates and by estimating the percentage excess mortality attributable to influenza.
Results. Age-standardized excess mortality rates were higher in South Africa than in the United States: 545 versus 133 deaths per 100,000 population for all causes (P < .001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza (P=.03). Standardization for nondemographic factors decreased but did not eliminate between-country differences; for example, the mean percentage of winter deaths attributable to influenza was 16% in South Africa and 6% in the United States (P < .001). For all respiratory causes, cerebrovascular disease, and diabetes, age-standardized excess death rates were 4—8-fold greater in South Africa than in the United States, and the percentage increase in winter deaths attributable to influenza was 2—4-fold higher.
Conclusions. These data suggest that the impact of seasonal influenza on mortality among elderly individuals may be substantially higher in an African setting, compared with in the United States, and highlight the potential for influenza vaccination programs to decrease mortality.
doi:10.1086/657314
PMCID: PMC3106243  PMID: 21070141
5.  Persistent High Burden of Invasive Pneumococcal Disease in South African HIV-Infected Adults in the Era of an Antiretroviral Treatment Program 
PLoS ONE  2011;6(11):e27929.
Background
Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008.
Methods
Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005–06 as the intermediate-HAART era and 2007–08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and–uninfected individuals.
Results
A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods.
Conclusion
Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults.
doi:10.1371/journal.pone.0027929
PMCID: PMC3225377  PMID: 22140487
6.  Nosocomial Outbreak of Novel Arenavirus Infection, Southern Africa 
Emerging Infectious Diseases  2009;15(10):1598-1602.
This case reinforces the need for strict screening of internationally transferred patients.
A nosocomial outbreak of disease involving 5 patients, 4 of whom died, occurred in South Africa during September–October 2008. The first patient had been transferred from Zambia to South Africa for medical management. Three cases involved secondary spread of infection from the first patient, and 1 was a tertiary infection. A novel arenavirus was identified. The source of the first patient’s infection remains undetermined.
doi:10.3201/eid1510.090211
PMCID: PMC2866397  PMID: 19861052
Arenavirus; Lujo virus; nosocomial infections; South Africa; Zambia; viruses; research
7.  Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005▿  
Journal of Clinical Microbiology  2008;46(10):3208-3214.
Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 μg/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Peni). Peni meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Peni was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P = 0.02). Pulsed-field gel electrophoresis grouped 63/82 Peni isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Peni isolates was not different from that of penicillin-susceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Peni isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Peni meningococcal isolates from sub-Saharan Africa.
doi:10.1128/JCM.00221-08
PMCID: PMC2566094  PMID: 18650361
8.  Epidemiology and Molecular Virus Characterization of Reemerging Rabies, South Africa 
Emerging Infectious Diseases  2007;13(12):1879-1886.
Late identification of an outbreak of human rabies in Limpopo Province led
The incidence of dog rabies in Limpopo Province, South Africa, increased from 5 cases in 2004 to 100 in 2006. Human rabies had last been confirmed in 1981, but investigations instituted after an index case was recognized in February 2006 identified 21 confirmed, 4 probable, and 5 possible human cases between August 5, 2005, and December 31, 2006. Twelve of these case-patients were identified retrospectively because the diagnosis of rabies was not considered: 6 of these patients consulted a traditional healer, 6 had atypical manifestations with prominent abdominal symptoms, and 6 of 7 patients tested had elevated liver enzyme activity. Molecular genetic analysis indicated that outbreak virus strains were most closely related to recent canine strains from southern Zimbabwe. Delayed recognition of the human cases may have resulted from decreased clinical suspicion after many years of effective control of the disease and the occurrence of atypical clinical presentations.
doi:10.3201/eid1312.070836
PMCID: PMC2874428  PMID: 18258039
Rabies; South Africa; outbreak; encephalitis; Limpopo; research
9.  Vaccine Effectiveness Estimates, 2004–2005 Mumps Outbreak, England 
Emerging Infectious Diseases  2007;13(1):12-17.
As vaccinated children approach adolescence, immunity wanes, which may contribute to outbreaks.
The United Kingdom and United States have recently experienced large outbreaks of mumps, which raises concerns about vaccine effectiveness. The effectiveness of the mumps component of the measles, mumps, rubella (MMR) vaccine was estimated using the screening method. In England from January 2004 through March 2005, 312 cases of mumps were reported in children eligible to have received 2 doses of MMR vaccine. Of these children, 52 (16.7%) had received 1 dose of MMR vaccine, and 97 (31.1%) had received 2 doses. Vaccine effectiveness was 88% (95% confidence interval [CI] 83%–91%) for 1 dose and 95% (95% CI 93%–96%) for 2 doses. The effectiveness of 1 dose declined from 96% (95% CI 81%–99%) in 2-year-olds to 66% (95% CI 30%–83%) in 11- to 12-year-olds, and the effectiveness of 2 doses declined from 99% (95% CI 97%–99.5%) in 5- to 6-year-olds to 86% (95% CI 74%–93%) in 11- to 12-year-olds (p<0.001 for 1 or 2 doses). Waning immunity may contribute to mumps outbreaks in older vaccinated populations.
doi:10.3201/eid1301.060649
PMCID: PMC2913658  PMID: 17370510
Measles; mumps; rubella vaccine; mumps; vaccine effectiveness; outbreak; England; research
10.  Adopting e-Learning Standards in Health Care: Competency-based Learning in the Medical Informatics Domain 
Like many forms of education, health professions education is increasingly competency-based. At the same time, there is growing use of e-learning technologies, which can be linked to competencies via emerging e-learning standards. Health care has been slow to adopt competencies and e-learning standards. We report our efforts to facilitate access to competencies and e-learning content in the medical informatics domain, linked by content-competency associations, based on standards developed by the MedBiquitous Consortium. We demonstrate that such standards can be successfully used and their implementation in other domains is warranted.
PMCID: PMC1839696  PMID: 17238358
11.  A Standards-Based Approach for Facilitating Discovery of Learning Objects at the Point of Care 
Recent concerns about the quality and safety of healthcare practice provide an imperative for discovering and accessing learning resources. The growing ubiquity of the Internet, World Wide Web, and on-line educational content provide opportunity for healthcare practitioners to identify and master learning in a granular and rapid fashion. The e-learning community at large has developed a number of standards to facilitate interoperability of learner competencies, metadata describing on-line content, and packaging and navigation of such content. The overall goal of our project is to enable healthcare professionals to easily and rapidly discover learning content at the point of care. This discovery and access of learning content will be based on healthcare-specific extensions of existing e-learning standards, which are themselves based on other Web standards, such as Web Services.
PMCID: PMC1560826  PMID: 16779266

Results 1-11 (11)