Molecular strain typing of the yaws pathogen, Treponema pallidum subspecies pertenue.

Yaws is a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue. The disease primarily affects children under 15 years of age living in low socioeconomic conditions in tropical areas. As a result of a renewed focus on the disease owing to a recent eradication effort initiated by the World Health Organization, we have evaluated a typing method, adapted from and based on the enhanced Centers for Disease Control and Prevention typing method for T. pallidum subsp. pallidum, for possible use in epidemiological studies. Thirty DNA samples from yaws cases in Vanuatu and Ghana, 11 DNA samples extracted from laboratory strains, and 3 published genomic sequences were fully typed by PCR/RFLP analysis of the tpr E, G, and J genes and by determining the number of 60-bp repeats within the arp gene. Subtyping was performed by sequencing a homonucleotide "G" tandem repeat immediately upstream of the rpsA gene and an 84-bp region of tp0548. A total of 22 complete strain types were identified; two strain types in clinical samples from Vanuatu (5q11/ak and 5q12/ak), nine strain types in clinical samples from Ghana (3q12/ah, 4r12/ah, 4q10/j, 4q11/ah, 4q12/ah, 4q12/v, 4q13/ah, 6q10/aj, and 9q10/ai), and twelve strain types in laboratory strains and published genomes (2q11/ae, 3r12/ad, 4q11/ad, 4q12/ad, 4q12/ag, 4q12/v, 5r12/ad, 6r12/x, 6q11/af, 10q9/r, 10q12/r, and 12r12/w). The tpr RFLP patterns and arp repeat sizes were subsequently verified by sequencing analysis of the respective PCR amplicons. This study demonstrates that the typing method for subsp. pallidum can be applied to subsp. pertenue strains and should prove useful for molecular epidemiological studies on yaws.

Integrated Mapping of Yaws and Trachoma in the Five Northern-Most Provinces of Vanuatu.

Yaws and trachoma are targeted for eradication and elimination as public health problems. In trachoma-endemic populations mass administration of azithromycin can simultaneously treat yaws. We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu, where trachoma and yaws are suspected to be co-endemic. Clinical signs of trachoma were evaluated using the WHO simplified grading system, and skin examination with a serological rapid diagnostic test used to identify yaws. We enrolled 1004 households in 59 villages over 16 islands, and examined 3650 individuals of all ages for trachoma. The overall adjusted prevalence of trachomatous inflammation-follicular (TF) in 1-9 year-olds was 12.0% (95% Confidence Interval: 8.1-16.7%), and the overall adjusted prevalence of TT in those aged 15 years and greater was 0.04% (95% CI 0-0.14%). In multivariate analysis, the odds of children having TF was 2.6 (95% CI = 1.5-4.4) times higher in households with unimproved latrines, and independently associated with the number of children in the household (OR 1.3, 95% CI = 1.0-1.6 for each additional child). We examined the skin of 821 children aged 5-14 years. Two children had yaws, giving an estimated prevalence of active yaws in those aged 5-14 years of 0.2% (95% CI = 0.03-0.9%). Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of yaws, integration of yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes.

Tropical leg ulcers in children: more than yaws.

The management of yaws has changed in recent years. Mass treatment with oral azithromycin has replaced intramuscular benzathine benzylpenicillin. Treponemal and non-treponemal serology (equivalent to TPHA and RPR) point-of-care blood testing is now available. In addition, recent studies in yaws endemic regions have shown that a significant number of leg ulcers in children which are clinically suggestive of yaws are caused by Haemophilus ducreyi. It is noteworthy that the World Health Organization has also set the ambitious goal to eliminate yaws by 2020.

Challenges and key research questions for yaws eradication.

Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.

Molecular differentiation of Treponema pallidum subspecies in skin ulceration clinically suspected as yaws in Vanuatu using real-time multiplex PCR and serological methods.

We developed a TaqMan-based real-time quadriplex polymerase chain reaction (PCR) to simultaneously detect Treponema pallidum subspecies pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum, the causative agents of venereal syphilis, yaws, and bejel, respectively. The PCR assay was applied to samples from skin ulcerations of clinically presumptive yaws cases among children on Tanna Island, Vanuatu. Another real-time triplex PCR was used to screen for the point mutations in the 23S rRNA genes that have previously been associated with azithromycin resistance in T. pallidum subsp. pallidum strains. Seropositivity by the classical syphilis serological tests was 35.5% among children with skin ulcerations clinically suspected with yaws, whereas the presence of T. pallidum subsp. pertenue DNA was only found in lesions from 15.5% of children. No evidence of T. pallidum subsp. pertenue infection, by either PCR or serology was found in ∼59% of cases indicating alternative causes of yaws-like lesions in this endemic area.

Impact of a targeted typhoid vaccination campaign following cyclone Tomas, Republic of Fiji, 2010.

After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June-December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to persons ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008-2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13-0.41; 0.24, 0.14-0.41; 0.58, 0.40-0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization.

Human leptospirosis in The Federated States of Micronesia: a hospital-based febrile illness survey.

BACKGROUND: Human leptospirosis is an emerging infectious disease of global significance, and is endemic to several countries in the Pacific. Zoonotic transmission dynamics combined with diagnostic challenges lead to difficulties in prevention and identification of cases. The Federated States of Micronesia (FSM) lacks surveillance data for human leptospirosis. This hospital-based serologic survey sought to estimate the burden of leptospirosis, collect information relating to associated factors, and assess the leptospirosis point-of-care rapid diagnostic test (RDT) commonly used in FSM. METHODS: A four-month hospital-based survey was conducted in Pohnpei State, FSM in 2011. Patients with undifferentiated fevers presenting to hospital were referred for enrolment by physicians. Consenting participants provided paired blood specimens 10-30 days apart, and responded to interview questions regarding demographics, clinical symptoms, exposure to animals, and environmental exposure. Blood samples were subjected to immunochromatographic RDT and confirmed by microscopic agglutination test (MAT). RESULTS: Of 54 participants tested by MAT, 20.4% (95% confidence interval [CI] 10.1-30.6%) showed serologic evidence of acute infection. Occupation student (odds ratio [OR], 17.5; 95% CI: 1.9-161.1) and recreational gardening (OR, 8.6; 95% CI: 1.0-73.8), identified by univariate logistic regression, were associated with infection. The local rapid diagnostic test (RDT) performed with a sensitivity of 69.2 (42.3-89.3 CI) and specificity of 90.0 (81.6-95.6 CI) compared to MAT. CONCLUSIONS: This study demonstrated a high burden of leptospirosis in Pohnpei. Further work is warranted to identify additional risk factors and opportunities to control leptospirosis in Pohnpei and other Pacific settings.

The Pacific experience: supporting small island countries and territories to meet their 2012 International Health Regulations (2005) commitments.

ISSUE: By 15 June 2012, States Parties to the International Health Regulations (2005), or IHR (2005), were required to have established the core capacities required to implement Annex 1 of IHR (2005). CONTEXT: The Pacific is home to 10 million people spread over 21 Pacific island countries and territories. Seven of those have populations of less than 25 000 people; 14 of the 21 Pacific island countries and territories are States Parties to the IHR (2005). ACTION: The World Health Organization Division of the South Pacific embarked on an initiative to support Pacific Island States Parties meet their 15 June 2012 IHR obligations. We adapted the 2012 IHR Monitoring Questionnaire (IHRMQ) to assist Pacific island countries and territories determine if they had met the capacities required to implement Annex 1 of the IHR (2005). If a Pacific island country or territory determined that it had not yet met the requirements, it could use the assessment outcome to develop a plan to address identified gaps. OUTCOME: Direct support was provided to 19 of 21 (91%) Pacific island countries and territories including 13 of 14 (93%) States Parties. Twelve of 14 (86%) fulfilled their requirements by 15 June 2012; those that had not yet met the requirements requested extensions and submitted plans describing how the IHR core capacities would be met. DISCUSSION: Adapting the 2012 IHRMQ for this purpose provided an efficient tool for assessing national capacity to implement Annex 1 of IHR (2005) and provided clear indication of what capacities required strengthening.

Typhoid fever: hurdles to adequate hand washing for disease prevention among the population of a peri-urban informal settlement in Fiji.

PROBLEM/CONTEXT: The Pacific island nation of Fiji Islands has high rates of endemic typhoid fever which is difficult to diagnose and often underreported. However, the majority of cases are preventable through use of safe water; adequate sanitation; vaccination; and, most sustainable of all, simple hygienic behaviour, such as hand washing with soap (HWWS). Despite many attempts by public health authorities, little progress has been made in the area of environmental adaptation and behaviour change. ACTION: To explore perceptions of typhoid fever risk among urban squatters and behavioural determinants surrounding HWWS, indigenous Fijians living in informal settlements with high typhoid fever incidence were invited to participate in focus group discussions. In-depth interviews were conducted with community leaders. OUTCOME: Perceptions of typhoid fever suggest confusion about risk factors, symptoms and communicability. Environmental barriers for hand washing were related to water and soap access. Standard social marketing approaches have been trialled with little clear evidence of impact. Despite this, we continue to advocate for the social and cultural determinants of typhoid prevention to remain central to future public health strategies. DISCUSSION: Despite behaviour change being notoriously difficult, we argue that community-driven behaviour adaptation initiatives based on sound epidemiological evidence and health communication theory are likely to have significant impact and greater likelihood of sustainability.

Influenza antiviral resistance in the Asia-Pacific region during 2011.

Despite greater than 99% of influenza A viruses circulating in the Asia-Pacific region being resistant to the adamantane antiviral drugs in 2011, the large majority of influenza A (>97%) and B strains (∼99%) remained susceptible to the neuraminidase inhibitors oseltamivir and zanamivir. However, compared to the first year of the 2009 pandemic, cases of oseltamivir-resistant A(H1N1)pdm09 viruses with the H275Y neuraminidase mutation increased in 2011, primarily due to an outbreak of oseltamivir-resistant viruses that occurred in Newcastle, as reported in Hurt et al. (2011c, 2012a), where the majority of the resistant viruses were from community patients not being treated with oseltamivir. A small number of influenza B viruses with reduced oseltamivir or zanamivir susceptibility were also detected. The increased detection of neuraminidase inhibitor resistant strains circulating in the community and the detection of novel variants with reduced susceptibility are reminders that monitoring of influenza viruses is important to ensure that antiviral treatment guidelines remain appropriate.

The Pacific experience: supporting small island countries and territories to meet their 2012 International Health Regulations (2005) commitments

Issue：By 15 June 2012, States Parties to the International Health Regulations (2005), or IHR (2005), were required to have established the core capacities required to implement Annex 1 of IHR (2005).Context：The Pacific is home to 10 million people spread over 21 Pacific island countries and territories. Seven of those have populations of less than 25 000 people; 14 of the 21 Pacific island countries and territories are States Parties to the IHR (2005).Action：The World Health Organization Division of the South Pacific embarked on an initiative to support Pacific Island States Parties meet their 15 June 2012 IHR obligations. We adapted the 2012 IHR Monitoring Questionnaire (IHRMQ) to assist Pacific island countries and territories determine if they had met the capacities required to implement Annex 1 of the IHR (2005). If a Pacific island country or territory determined that it had not yet met the requirements, it could use the assessment outcome to develop a plan to address identified gaps.Outcome：Direct support was provided to 19 of 21 (91%) Pacific island countries and territories including 13 of 14 (93%) States Parties. Twelve of 14 (86%) fulfilled their requirements by 15 June 2012; those that had not yet met the requirements requested extensions and submitted plans describing how the IHR core capacities would be met.Discussion：Adapting the 2012 IHRMQ for this purpose provided an efficient tool for assessing national capacity to implement Annex 1 of IHR (2005) and provided clear indication of what capacities required strengthening.

Pacific-wide simplified syndromic surveillance for early warning of outbreaks.

The International Health Regulations require timely detection and response to outbreaks. Many attempts to set up an outbreak early warning system in Pacific island countries and territories (PICTs) have failed. Most were modelled on systems from large countries; large amounts of data often overwhelmed small public health teams. Many conditions required overseas laboratory confirmation, further reducing timeliness and completeness. To improve timeliness and reduce the data burden, simplified surveillance was proposed, with case definitions based on clinical signs and symptoms without the need for laboratory confirmation or information on symptoms, location, sex and age. After trials in three PICTs, this system was implemented throughout the Pacific. Enthusiastic adoption by public health staff resulted in 20 of 22 PICTs reporting weekly to the World Health Organization within 12 months of starting to use the system. In the first year, the system has detected many infectious disease outbreaks and facilitated timely implementation of control measures. For several Pacific countries and territories, this is the first functional and timely infectious disease surveillance system. When outbreak detection is the principal objective, simplification of surveillance should be a priority in countries with a limited public health system capacity.

Sustaining surveillance: evaluating syndromic surveillance in the Pacific.

Prior to the 2009 H1N1 pandemic, the Pacific Island Countries and Territories (PICTs) had agreed to develop a standardised, simple syndromic surveillance system to ensure compliance with International Health Regulations requirements (rapid outbreak detection, information sharing and response to outbreaks). In October 2010, the new system was introduced and over the next 12 months implemented in 20 of 22 PICTs. An evaluation was conducted to identify strengths and weaknesses of the system, ease of use and possible points for improvement. An in-country quantitative and qualitative evaluation in five PICTs identified that the most important determinants of the system's success were: simplicity of the system; support from all levels of government; clearly defined roles and responsibilities; feedback to those who collect the data; harmonisation of case definitions; integration of data collection tools into existing health information systems; and availability of clinical and epidemiological advice from external agencies such as the World Health Organization and the Secretariat of the Pacific Community. Regional reporting of alerts, outbreaks and outbreak updates has dramatically increased since implementation of the system. This syndromic system will assist PICTs to detect future influenza pandemics and other emerging infectious diseases and to rapidly contain outbreaks in the Pacific.

Use of serum and blood samples on filter paper to improve the surveillance of Dengue in Pacific Island Countries.

BACKGROUND: In Pacific Island Countries (PICs) the epidemiology of dengue is characterized by long-term transmission of a single dengue virus (DENV) serotype. The emergence of a new serotype in one island country often indicates major outbreaks with this serotype will follow in other PICs. OBJECTIVES: Filter paper (FP) cards on which whole blood or serum from dengue suspected patients had been dried was evaluated as a method for transportation of this material by standard mail delivery throughout the Pacific. STUDY DESIGN: Twenty-two FP-dried whole blood samples collected from patients in New Caledonia and Wallis & Futuna Islands, during DENV-1 and DENV-4 transmission, and 76 FP-dried sera collected from patients in Yap State, Majuro (Republic of Marshall Islands), Tonga and Fiji, before and during outbreaks of DENV-2 in Yap State and DENV-4 in Majuro, were tested for the presence of DENV RNA, by serotype specific RT-PCR, at the Institut Louis Malardé in French Polynesia. RESULTS: The serotype of DENV could be determined, by a variety of RT-PCR procedures, in the FP-dried samples after more than three weeks of transport at ambient temperatures. In most cases, the sequencing of the envelope gene to genotype the viruses also was possible. CONCLUSIONS: The serotype and genotype of DENV can be determined from FP-dried serum or whole blood samples transported over thousands of kilometers at ambient, tropical, temperatures. This simple and low-cost approach to virus identification should be evaluated in isolated and resource poor settings for surveillance for a range of significant viral diseases.

A standardized process for developing a national notifiable diseases list in a pacific island setting.

The authors describe an adapted method, originally developed for infectious disease resource allocation, for prioritizing infectious diseases for inclusion in a Pacific island nation's National Notifiable Diseases List. Using a process that was systematic, transparent, objective, and addressed multiple criteria, a panel of stakeholders judged candidate diseases against 12 objective criteria and arrived at weighted scores for the diseases, which were then ranked. The result was the successful creation of a list of 22 urgently notifiable conditions. However, the process was only incrementally more useful than the use of consensus, and certain anomalies necessitated a reality check and adjustment of the final results. The process described herein may be more useful in settings where there is wide disagreement among stakeholders; it also appears more useful for its original purpose-prioritizing public health resource allocation for infectious disease control. The modifications discussed may make it more relevant to notifiable disease selection.

Investigation and control of an outbreak of Enterobacter aerogenes bloodstream infection in a neonatal intensive care unit in Fiji.

Ten neonates developed blood stream infection with extended-spectrum beta-lactamase-producing Enterobacter aerogenes in a neonatal intensive care unit in Fiji. The source of the outbreak was traced to a bag of contaminated normal saline in the ward, which was used for multiple patients. All isolates recovered from patients were indistinguishable from the bacteria recovered from the normal saline by pulsed-field gel electrophoresis. The outbreak was controlled using simple infection control practices such as reinforcement of strict hand hygiene policy, provision of single use vials of normal saline, and strict aseptic technique for injections.

Zika virus outbreak on Yap Island, Federated States of Micronesia.

BACKGROUND: In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. METHODS: We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. RESULTS: We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. CONCLUSIONS: This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.

Protective effect of maritime quarantine in South Pacific jurisdictions, 1918-19 influenza pandemic.

We reviewed mortality data of the 1918-19 influenza pandemic for 11 South Pacific Island jurisdictions. Four of these appear to have successfully delayed or excluded the arrival of pandemic influenza by imposing strict maritime quarantine. They also experienced lower excess death rates than the other jurisdictions that did not apply quarantine measures.

Pneumonic plague cluster, Uganda, 2004.

The public and clinicians have long-held beliefs that pneumonic plague is highly contagious; inappropriate alarm and panic have occurred during outbreaks. We investigated communicability in a naturally occurring pneumonic plague cluster. We defined a probable pneumonic plague case as an acute-onset respiratory illness with bloody sputum during December 2004 in Kango Subcounty, Uganda. A definite case was a probable case with laboratory evidence of Yersinia pestis infection. The cluster (1 definite and 3 probable cases) consisted of 2 concurrent index patient-caregiver pairs. Direct fluorescent antibody microscopy and polymerase chain reaction testing on the only surviving patient's sputum verified plague infection. Both index patients transmitted pneumonic plague to only 1 caregiver each, despite 23 additional untreated close contacts (attack rate 8%). Person-to-person transmission was compatible with transmission by respiratory droplets, rather than aerosols, and only a few close contacts, all within droplet range, became ill.

Persistent Yersinia pestis antigens in ischemic tissues of a patient with septicemic plague.

In November 2002, a couple from New Mexico traveled to New York where both had fever and unilateral inguinal adenopathy. The husband was in septic shock when he sought medical care and was admitted to an intensive care unit, where he developed ischemic necrosis of his feet which later required bilateral amputation. Yersinia pestis was grown from his blood. Immunohistochemical assays using anti-Y pestis antibodies demonstrated multiple bacteria and granular antigens in and around vessels of the ischemic amputation tissues obtained 20 days after initiation of antibiotics; however, no evidence of Y pestis was present in viable tissues. Immunohistochemical evidence of Y pestis inside vessels of gangrenous feet in this patient underscores the importance of adequate excision of necrotic or partially necrotic tissues because antibiotics cannot be effectively delivered to necrotic and poorly perfused tissues.