PHILADELPHIA — An IDWeek 2014 symposium titled “Hot Topics in the Tropics” covered a broad range of viral and bacterial infections endemic to tropical regions of the world. Daniel Bausch, MD, MPH, of Tulane University School of Public Health and Tropical Medicine and of the US Naval Medical Research Unit No. 6 in Lima, Peru; Yukari Manabe, MD, of Johns Hopkins University; and Beth Kirkpatrick, MD, of the University of Vermont College of Medicine, presented findings and analysis on the management of tropical diseases and larger trends in epidemiology and antimicrobial resistance. Infectious Disease News compiled a list of the 10 most important take-home messages from the session.
“When this was reported in April, people would have said that it was not completely unexpected,” Bausch said. “When we found that it was the Zaire species, there was some speculation on how it got there.”
Some experts believe it may have come from a migratory bat, but Bausch said the mode of transmission, like many other aspects of the Ebola outbreak, remains undetermined.
“Interpreting seroprevalence data is half science and half art,” he said. “There are no definite answers but there is some suggestion that this may have been here for a while.”
Bausch said that nosocomial infections likely played a part in the spread of Ebola. He added that when the virus reached Conakry, the capital of Guinea, it was the first time the infection had been seen in a major urban area.
Traditionally, health care organizations have employed an intense 2- to 3-month comprehensive approach to crush Ebola outbreaks. “We are used to declaring victory within 3 to 4 months,” he said. “The duration and scale of the current outbreak has outstripped the resources of international organizations.”
Bausch said a massive upscaling is required to combat the current epidemic. Changes need to occur regarding leadership and surveillance at the top level and communication and education on the local level. He said entire villages should be isolated and monitored if necessary, and the clinical community should be accelerating use of experimental treatments and vaccines.
However, Bausch remains somewhat hopeful. “This outbreak has been way overblown in terms of whether it will become airborne,” he said. “But ultimately we will have to transfer the capacity for containment to local people on the ground.”
Dengue virus vaccine
Bausch discussed encouraging phase 3 data from Capeding and colleagues, who investigated the live attenuated tetravalent vaccine in approximately 10,000 children aged 2 to 14 years. The vaccine was compared with placebo.
“Results showed vaccine efficacy of 56%,” he said. “Whether you consider that good or bad is one of those glass-half-full, glass-half-empty discussions.”
He said the effect of the vaccine varied by serotype, with 35% efficacy in serotype 2 and almost 80% for serotype 3. “There were a few serious adverse events in both vaccines and controls,” Bausch said.
“They concluded that the vaccine is safe and moderately efficacious,” he added. “Given how many cases of dengue there are around the world, something that protects 56% of kids might be useful.”
Findings for the vaccine in a cohort of approximately 20,000 children from Latin America are forthcoming, Bausch said.
MERS, coronavirus and camels
The relationship between Middle East respiratory syndrome, or MERS, coronavirus in camels and humans remains unclear, according to Bausch. He described a case that was fatal in a man who kept nine camels. Evidence suggests, however, that the camels were infected and then cleared the infection on their own.
“The evidence points to zoonotic infection of a human from a dromedary camel,” Bausch said. “However, the fact that the camels appear to have been sick and cleared the virus suggests that they are not the natural reservoir. They may be an intermediary host.”
Bausch offered bats as a potential alternative mode of transmission.
Chikungunya and polio eradication
Bausch said that chikungunya has been reported in the Americas for the first time. “We had never seen it in this hemisphere before this year,” he said, citing the Aedes mosquito as a mode of transmission. “Millions and millions of cases swept across the world.”
Regarding the state of polio eradication, Bausch said there were 209 cases reported in Afghanistan, Pakistan and Nigeria this year, down from 284 cases last year. “At this point, controlling polio is much less a scientific challenge than a political and social one,” he said. “We are dealing with areas of great civil unrest.”
Understanding resistance trends
Manabe highlighted the underreporting of multidrug-resistant tuberculosis as an indicator of broader trends in antimicrobial resistance. She noted a number of large studies, including an investigation by Leopold and colleagues that described antibiotic resistance trends in everything from Klebsiella pneumoniae to Staphylococcus aureus. “For example, there is not very good susceptibility to cotrimoxazole in E. coli in Africa,” she said.
Clinicians should be aware of resistance trends by location, according to Manabe. “You have to know where you stand in your specific area,” she said, noting, for example, that there is very little antibiotic resistance in Salmonella enterica serovar Typhi in Indonesia but high rates of multidrug resistance in Vietnam.
High mortality rates associated with K. pneumoniae “could be a harbinger for the future,” Manabe said, largely because of poor reporting. “Many tropical zones are not represented on any epidemiological or surveillance map because there is no information,” she said. “We need to know where our drug resistance epidemics are.”
Manabe highlighted data indicating a 21% increase in Neisseria gonorrhoeae incidence between 2005 and 2008.
“We are seeing increasing resistance to all antibiotics in this infection,” she said. “It is resistant to penicillins, tetracyclines, spectinomycin, narrow-spectrum cephalosporins, amphenicols, TMP-SMX, macrolides and fluoroquinolones.”
Findings from Unemo and colleagues suggest that if the trend continues, gonorrhea could reach “superbug” status, according to Manabe. She encouraged clinicians to take a broad view of resistance patterns in this disease. “You can look in your own yard, but maybe you need to look in someone else’s yard to find out where the resistance trends are happening,” she said.
Thailand Smart Use program
Not all of the news is bad with regard to antimicrobial resistance, according to Manabe. She highlighted the Smart Use program in Thailand as something of a success story.
“They decided to intervene on the supply side and on the demand side,” she said, noting that clinicians were encouraged to find other ways to treat conditions ranging from upper respiratory infections to diarrhea and wound infections. “Clinicians worked with policymakers to target organizations all the way up to the policy level.”
Manabe pointed out an 18% to 46% reduction in antibiotic use in 3 target areas (upper respiratory infection, diarrhea and simple wound infections), with 97% of targeted patients recovering. She added that there are more than 600 health centers participating.
“With this kind of volume, it will be interesting to see how their resistance patterns change over time,” she said. “But the next step will be to talk to patients who are used to getting antibiotics over the counter. It will be a challenge to enact this kind of change at the social level.”
“Malaria control takes steps forward and backward,” Kirkpatrick said.
She noted that, according to the 2013 World Malaria Report, incidence rates have decreased by 25% and mortality decreased by 42% since the year 2000. “Funding rose from $100 million to $1.94 billion,” she said. “This is an incredible increase in support for the malaria community.”
Increasing rates of artemisinin resistant infections in Southeast Asia, however, tempered her enthusiasm.
A new drug, cipargamin, may be a new approach, according to Kirkpatrick. “This drug is in the very early stages, but it is the type of drug the malaria community would like to see more of,” she said, noting that the drug inhibits a Na+-ATPase in sodium/osmotic homeostasis, is active against sexual and asexual stages and has demonstrated efficacy in the setting of kelch mutations.
In other treatment advances, tafenoquine was granted breakthrough drug status by the FDA for the prevention of Plasmodium vivax relapse. Also, the GlaxoSmithKline recombinant vaccine demonstrated 45% efficacy in an intention-to-treat analysis among children, but efficacy waned significantly over 18 months.
Kirkpatrick suggested that Cryptosporidium is “back in the limelight.”
She described the parasite as “ubiquitous,” and highlighted findings from the GEMS study in The Lancet in 2013. “This multi-site study looked at etiologic agents causing moderate or severe diarrhea in developing countries,” she said. “Surprisingly, Cryptosporidium was one of the top causes in infants and young children. “It wasn’t that we didn’t realize that it caused significant diarrhea disease, but its relative importance had been unrecognized.”
Kirkpatrick said that in light of the substantial burden of disease, the research community is coming to understand the challenges presented by Cryptosporidium, and is moving toward better diagnostics and therapeutics. “This data has revitalized the research community,” she said. “We are gaining a better understanding of the burden of cryptosporidiosis, including the impact of co-pathogens, the role of malnutrition and gut inflammation in this disease.”
She raised the question of whether a case could be made for a vaccine. “There is still a lot to learn about Cryptosporidium before a vaccine could be considered for development,” she said.
Neglected tropical diseases
Kirkpatrick discussed the importance of neglected parasitic tropical diseases that remain underappreciated and underfunded, particularly in the face of larger challenges presented by Ebola and antimicrobial resistance. The list included Chagas disease, leishmaniasis, African trypanosomiasis and schistosomiasis.
New data and a report in the New York Times has “reiterated the important association of female genital schistosomiasis and HIV transmission in Sub-Saharan Africa,” she said. She also reminded clinicians that many neglected tropical diseases are seen in the Southern United States, including Chagas disease, toxocariasis, cysticercosis, and toxoplasmosis.
Disclosure: Bausch, Kirkpatrick and Manabe report no relevant financial disclosures.
For more information:
Capeding RM. Lancet. 2014;384:1358-1365.
Kotloff KL. Lancet. 2014;382:209-222.
Leopold SJ J Antimicrob Chemother.2014;69:2337-2353.
Sumpradit N. Bull World Health Organ. 2012;90:905-913.
Unemo M. Clin Microbiol Rev. 2014;27:587-613.