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Phylogenetic Analysis of an Unusual Increase in Salmonella enterica serovar Paratyphi A Infection among Travelers Returning from Myanmar

Abstract Background The proportion of enteric fever cases caused by Salmonella enterica subspecies enterica serovar Paratyphi A (S. Paratyphi A) has recently been increasing in Asian counties, which is a public health concern. In 2015, an unusual increase in S. Paratyphi A infection among Japanese travelers returning from Myanmar was noted, while there is little information on this uptrend in Myanmar. Methods Isolates from travelers who returned with enteric fever from 2005 to 2015 were analyzed in order to determine country-specific notification rates (epidemiological investigation). The notification rate was defined as cases returning from each country per 100,000 Japanese travelers who visited to the country. S. Paratyphi A isolates collected from 2001 to 2015 were analyzed by whole-genome sequencing (microbiological investigation). Results Yearly notification trends indicated that enteric fever was potentially endemic to Myanmar (5–16 cases/100,000 travelers); the trends were similar to those observed in India (4–21 cases/100,000 travelers). A rapid increase in S. Paratyphi A infection occurred from 2012–2014 (2–4 cases/100,000 travelers) to 2015 (13 cases/100,000 travelers). A phylogenetic tree, constructed based on analysis of 105 S. Paratyphi A isolates (33 and 30 related to Myanmar and Cambodia, and 42 controls), revealed that most Myanmar- and Cambodia-related isolates formed clusters in the same lineage (Figure 1). Additionally, Myanmar-related isolates from 2015 harbored identical phage type 1 and were genetically closely related [each isolates had 0–10 single-nucleotide polymorphisms (SNPs), mostly within 0–7 SNPs] (Figure 2), yielding a wider SNP range than outbreak-associated isolates from Cambodia in 2013 (within a SNP distance of 0–6). Conclusion Epidemiological trends and molecular subtyping suggested a possible outbreak of S. Paratyphi A infection occurred in Myanmar in 2015. The recent uptrend of S. Paratyphi Ainfection in Myanmar is important for travelers and clinicians since infection cannot be prevented by typhoid vaccination. Figure 1. Polygenetic tree of 105 S. Paratyphi A isolates Figure 2. SNP analyses of S. Paratyphi A isolates from Myanmar in 2015 (A) and Cambodia in 2013 (B). Disclosures All authors: No reported disclosures.

Background. As wild poliovirus is eradicated and countries switch from Oral Polio Vaccine (OPV) to Inactivated Polio Vaccine (IPV) per WHO recommendations, preventing circulation of vaccine-derived poliovirus is a top priority. However, spatial dynamics of OPV transmission are not well understood. Understanding these trends will improve resource targeting in the event of OPV reintroduction in undervaccinated communities. Mexico provides a natural environment to study OPV as it provides IPV routinely and bi-annual OPV campaigns.
Methods. Children in three villages near Orizaba, Mexico were randomized to three levels (10%, 30%, 70%) to receive OPV. We measured distance to nearest OPV shedding, and the amount of shedding close to unvaccinated individuals. We used maps to show the proximity and amount of shedding. Distance and density of shedding was analyzed separately using mixed effects logistic regression with random effects for household and time, adjusted for age, gender, area, and running water.
Results. The median distance to nearest OPV shedding was 85 meters (IQR 46,145). The median number of shedding individuals within 200m was 3 (2, 6). Shedding and between household transmission occurred rapidly with unvaccinated individuals shedding on day one of the study (Figure 1). There was little evidence (Odds Ratio [OR] 1.04 (95% Highest Posterior Density [HPD] 0.92, 1.16)) of an association between distance (per 100 m) from OPV shedding and odds of shedding. There was some suggestion that the number of OPV shedding within 200 m may have some effect on unvaccinated shedding with OR 0.93 (HPD 0.·84, 1·01) but not at 100 or 500m. Results were consistent across the three villages.
Conclusion. Household structure appears to have limited value in predicting transmission of poliovirus shedding. The use of OPV results in rapid but low levels of transmission throughout the community and this would usually go undetected. The only way to avoid this is to not use OPV or to have strong controls such as quarantine, or strict hygiene protocols. After withdrawal of OPV worldwide the decision to reintroduce due to an outbreak should not be taken lightly as it appears a small amount of OPV is needed to result in transmission. Background. The proportion of enteric fever cases caused by Salmonella enterica subspecies enterica serovar Paratyphi A (S. Paratyphi A) has recently been increasing in Asian counties, which is a public health concern. In 2015, an unusual increase in S. Paratyphi A infection among Japanese travelers returning from Myanmar was noted, while there is little information on this uptrend in Myanmar.
Methods. Isolates from travelers who returned with enteric fever from 2005 to 2015 were analyzed in order to determine country-specific notification rates (epidemiological investigation). The notification rate was defined as cases returning from each country per 100,000 Japanese travelers who visited to the country. S. Paratyphi A isolates collected from 2001 to 2015 were analyzed by whole-genome sequencing (microbiological investigation).
Results. Yearly notification trends indicated that enteric fever was potentially endemic to Myanmar (5-16 cases/100,000 travelers); the trends were similar to those observed in India (4-21 cases/100,000 travelers). A rapid increase in S. Paratyphi A infection occurred from 2012-2014 (2-4 cases/100,000 travelers) to 2015 (13 cases/100,000 travelers). A phylogenetic tree, constructed based on analysis of 105 S. Paratyphi A isolates (33 and 30 related to Myanmar and Cambodia, and 42 controls), revealed that most Myanmar-and Cambodia-related isolates formed clusters in the same lineage (Figure 1). Additionally, Myanmar-related isolates from 2015 harbored identical phage type 1 and were genetically closely related [each isolates had 0-10 single-nucleotide polymorphisms (SNPs), mostly within 0-7 SNPs] (Figure 2), yielding a wider SNP range than outbreak-associated isolates from Cambodia in 2013 (within a SNP distance of 0-6).  Disclosures. All authors: No reported disclosures. Methods. We reviewed records of 101 patients in three hospitals in Hidalgo County, Texas, who had positive typhus serology (IgG or IgM titer ≥1:128) during 3 years, 2014-2016 and were categorized as suspected, probable or confirmed murine typhus cases in accord with CDC definitions. We excluded 11 cases because a concurrent infection may have confounded our tabulation of manifestations or there was insufficient information to make a clinical diagnosis.

Murine Typhus: a Common Cause of Acute Febrile Illness with Potential for Serious Complications
Results. The majority presented with typical typhus: fever, headache, myalgias and fatigue. Rash, thrombocytopenia and elevated hepatic transaminases were frequent (Table). Clinical complications in 25 cases (28%) caused a less typical syndrome, including bronchiolitis, pneumonia, pancreatitis, cholecystitis, mesenteric adenitis, myositis, rhabdomyolysis, meningitis and septic shock. Procalcitonin was >0.5 in 10 of 14 (71%) cases. Once the diagnosis was suspected, patients were treated with doxycycline with a rapid response in every case. Generally fever disappeared within 24-36 hours of the first dose.
Conclusion. Murine typhus is a common endemic infection in South Texas. Although most patients had a typical syndrome, the disease is multisystem, and complications appeared in 28% of cases. Procalcitonin was usually elevated. Rats and opossums are common reservoirs for Rickettsia typhi, and a search for cases of murine typhus may be warranted in other parts of the US as well, so that treatment with doxycycline can be begun promptly.
Disclosures. All authors: No reported disclosures.