David N. Durrheim

Case Definitions, Diagnostic Algorithms, and Priorities in Encephalitis: Consensus Statement of the International Encephalitis Consortium

BACKGROUND Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. METHODS In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. RESULTS We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. CONCLUSIONS We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia

Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.

Using the SaTScan method to detect local malaria clusters for guiding malaria control programmes

BackgroundMpumalanga Province, South Africa is a low malaria transmission area that is subject to malaria epidemics. SaTScan methodology was used by the malaria control programme to detect local malaria clusters to assist disease control planning. The third season for case cluster identification overlapped with the first season of implementing an outbreak identification and response system in the area.MethodsSaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using definitively confirmed individual cases in seven towns over three malaria seasons. Following passive case reporting at health facilities during the 2002 to 2005 seasons, active case detection was carried out in the communities, this assisted with determining the probable source of infection. The distribution and statistical significance of the clusters were explored by means of Monte Carlo replication of data sets under the null hypothesis with replications greater than 999 to ensure adequate power for defining clusters.Results and discussionSaTScan detected five space-clusters and two space-time clusters during the study period. There was strong concordance between recognized local clustering of cases and outbreak declaration in specific towns. Both Albertsnek and Thambokulu reported malaria outbreaks in the same season as space-time clusters. This synergy may allow mutual validation of the two systems in confirming outbreaks demanding additional resources and cluster identification at local level to better target resources.ConclusionExploring the clustering of cases assisted with the planning of public health activities, including mobilizing health workers and resources. Where appropriate additional indoor residual spraying, focal larviciding and health promotion activities, were all also carried out.

Increased Gametocytemia after Treatment: An Early Parasitological Indicator of Emerging Sulfadoxine-Pyrimethamine Resistance in Falciparum Malaria

BACKGROUND Although malaria treatment aims primarily to eliminate the asexual blood stages that cause illness, reducing the carriage of gametocytes is critical for limiting malaria transmission and the spread of resistance. METHODS Clinical and parasitological responses to the fixed-dose combination of sulfadoxine and pyrimethamine in patients with uncomplicated falciparum malaria were assessed biannually since implementation of this treatment policy in 1998 in Mpumalanga Province, South Africa. RESULTS Despite sustained cure rates of > 90% (P = .14), the duration of gametocyte carriage increased from 3 to 22 weeks (per 1000 person-weeks) between 1998 and 2002 (P < .001). The dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance were the most important drivers of the increased gametocytemia, although these mutations were not associated with increased pretreatment asexual parasite density or slower asexual parasite clearance times. The geometric mean gametocyte duration and area under the gametocyte density time curve (per 1000 person-weeks) were 7.0 weeks and 60.8 gametocytes/microL per week, respectively, among patients with wild-type parasites, compared with 45.4 weeks (P = .016) and 1212 gametocytes/microL per week (P = .014), respectively, among those with parasites containing 1-5 dhfr/dhps mutations. CONCLUSIONS An increased duration and density of gametocyte carriage after sulfadoxine-pyrimethamine treatment was an early indicator of drug resistance. This increased gametocytemia among patients who have primary infections with drug-resistant Plasmodium falciparum fuels the spread of resistance even before treatment failure rates increase significantly.

Etiology of encephalitis in Australia, 1990-2007.

Unexplained disease etiology in hospitalized patients highlights the importance of surveillance to detect emerging novel pathogens.

Understanding the community impact of lymphatic filariasis: a review of the sociocultural literature

Lymphatic filariasis (LF) is endemic in approximately 80 tropical and subtropical countries. About 120 million people are infected with the parasite and a billion are estimated to be at risk of infection. The main focus of the LF elimination programme to date has been to interrupt transmission by means of annual community-wide treatment campaigns with diethylcarbamazine and albendazole, or albendazole and ivermectin, for a period of four to six years. Although substantial progress has been recorded wherever the strategy has been successfully implemented, initial gains have been accompanied by a realization that this strategy alone will not ensure a permanent solution in all settings. The fairly extensive LF literature is dominated by laboratory research and quantitative field measurement of the impact of LF, particularly local prevalence studies of parasite-infected humans and vectors. As the global elimination programme expands, the absence of sociocultural understanding is being recognized as a critical flaw in ensuring that programmes are appropriate and responsive to local needs and understanding. This paper assesses the current state of sociocultural understanding pertaining to LF. It concludes that, at present, there is insufficient understanding of the sociocultural factors associated with the presence and treatment of the disease, and that appropriate social science methods should be used to address this deficiency and ensure community partnership in delivering and sustaining the success of LF elimination programmes.

Evidence supporting zoonotic transmission of Cryptosporidium in rural New South Wales

Cryptosporidium hominis, which has an anthroponotic transmission cycle and Cryptosporidium parvum, which is zoonotic, are the primary species of Cryptosporidium that infect humans. The present study identified the species/genotypes and subgenotypes of Cryptosporidium in 7 human and 15 cattle cases of sporadic cryptosporidiosis in rural western NSW during the period from November 2005 to January 2006. The species/genotype of isolates was determined by PCR sequence analysis of the 18S rRNA and C. parvum and C. hominis isolates were subgenotyped by sequence analysis of the GP60 gene. Fourteen of 15 cattle-derived isolates were identified as C. parvum and 1 as a C. bovis/C. parvum mixture. Of the human isolates, 4 were C. parvum and 3 were C. hominis. Two different subgenotypes were identified with the human C. hominis isolates and six different subgenotypes were identified within the C. parvum species from humans and cattle. All four of the C. parvum subtypes found in humans were also found in the cattle, indicating that zoonotic transmission may be an important contributor to sporadic human cases cryptosporidiosis in rural NSW.

Measles - The epidemiology of elimination.

Tremendous progress has been made globally to reduce the contribution of measles to the burden of childhood deaths and measles cases have dramatically decreased with increased two dose measles-containing vaccine coverage. As a result the Global Vaccine Action Plan, endorsed by the World Health Assembly, has targeted measles elimination in at least five of the six World Health Organisation Regions by 2020. This is an ambitious goal, since measles control requires the highest immunisation coverage of any vaccine preventable disease, which means that the health system must be able to reach every community. Further, while measles remains endemic in any country, importations will result in local transmission and outbreaks in countries and Regions that have interrupted local endemic measles circulation. One of the lines of evidence that countries and Regions must address to confirm measles elimination is a detailed description of measles epidemiology over an extended period. This information is incredibly valuable as predictable epidemiological patterns emerge as measles elimination is approached and achieved. These critical features, including the source, size and duration of outbreaks, the seasonality and age-distribution of cases, genotyping pointers and effective reproduction rate estimates, are discussed with illustrative examples from the Region of the Americas, which eliminated measles in 2002, and the Western Pacific Region, which has established a Regional Verification Commission to review progress towards elimination in all member countries.

A multi-state outbreak of Salmonella Saintpaul in Australia associated with cantaloupe consumption

A multi-state outbreak of Salmonella enterica serovar Saintpaul infection occurred in Australia during October 2006. A case-control study conducted in three affected jurisdictions, New South Wales, Victoria and Australian Capital Territory, included 36 cases with the outbreak-specific strain of S. Saintpaul identified by multiple locus variable-number tandem repeat analysis (MLVA) in a faecal specimen and 106 controls. Consumption of cantaloupe (rockmelon) was strongly associated with illness (adjusted OR 23.9 95%, 95% CI 5.1-112.4). S. Saintpaul, with the outbreak MLVA profile, was detected on the skin of two cantaloupes obtained from an implicated retailer. Trace-back investigations did not identify the specific source of the outbreak strain of S. Saintpaul, but multiple Salmonella spp. were detected in environmental samples from farms and packing plants investigated during the trace-back operation. Cantaloupe production and processing practices pose a potential public health threat requiring regulatory and community educational interventions.

Efficacy of three insect repellents against the malaria vector Anopheles arabiensis

Three commercial repellents marketed in South Africa: Bio‐SkincareTM (BSC, oils of coconut, jojoba, rapeseed and vitamin E), MosiguardTM towelletes with 0.574 g quwenling (p‐menthane‐3,8‐diol, PMD) and the standard deet (15% diethyl‐3‐methylbenzamide, TabardTM lotion), were compared against a laboratory colony of the mosquito Anopheles arabiensis Patton (Diptera: Culicidae), the predominant malaria vector in South Africa. Human forearms were treated with 1.2 g BSC, 0.8 g PMD towelette or 0.5 g deet and exposed to 200 hungry An. arabiensis females for 1 min, at intervals of 1–6 h post‐treatment. Tests were conducted by three adult male volunteers (aged 30–45 years, crossover controlled test design for 3 consecutive days), using their left arm for treatment and right arm for untreated control. Biting rates averaged 39–52 bites/min on untreated arms. All three repellents provided complete protection against An. arabiensis for up to 3–4 h post‐application; deet and PMD gave 90–100% protection up to 5–6 h, but BSC declined to only 52% protection 6 h post‐treatment. These results are interpreted to show that all three repellent products give satisfactory levels of personal protection against An. arabiensis for 4–5 h, justifying further evaluation in the field.