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Ensuring resistance doesn’t take hold: The importance of taking on typhoid now

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PATH/Monique Berlier

Typhoid may seem like a distant memory in industrialized countries, but for many low- and middle-income countries it continues to cause millions of illnesses and about 150,000 deaths per year. New tools are needed to combat this looming threat.

June 14, 2017 by Dr. Kathleen Neuzil

Typhoid may seem like a distant memory in industrialized countries, but for many low- and middle-income countries (LMICs) it continues to cause millions of illnesses and about 150,000 deaths per year in endemic areas and during outbreaks. Spread through contaminated food and water, typhoid typically burdens young children and adolescents under the age of 15. Recently, we have witnessed several outbreaks, including those in Zimbabwe,  Zambia, and Pakistan, where thousands of typhoid cases have been reported.

Without treatment, typhoid can cause serious short- and long- term complications, and even lead to death. While antibiotic treatment has greatly improved outcomes in typhoid patients, the effectiveness of antibiotics is becoming increasingly limited. The World Health Organization (WHO) has called antibiotic resistance one of the biggest threats to global health today, and treating typhoid is no exception. Drug and multi-drug resistant typhoid has been increasingly reported in LMICs in Southeast Asia and sub-Saharan Africa where typhoid burdens are highest, and treating drug-resistant typhoid may become prohibitively expensive.

As global experts met this week at the International Caparica Conference in Antibiotic Resistance to discuss ways to address this growing issue, I reflected on ways that we can combat this looming threat for typhoid:

1. We need to accelerate the introduction of typhoid vaccines alongside proven water, sanitation, and hygiene (WASH) interventions.

Just as we know how to treat typhoid, we also know how to prevent it: WASH precautions are key. However, given the significant burden of typhoid among hard-to-reach populations where WASH progress may be slow, we need an integrated approach to prevention that includes vaccines. Currently, two vaccines are globally available and are effective in preventing typhoid—an oral live attenuated vaccine and an injectable Vi capsular polysaccharide vaccine. In 2008, WHO recommended that both vaccines can be used during outbreaks and in endemic areas, but uptake has been low and neither are used routinely.

Newer typhoid conjugate vaccines (TCVs) have the potential to overcome the shortcomings of the current vaccines by allowing for longer-lasting protection, fewer doses, and greater suitability for children younger than two years old in routine childhood immunization programs. The Typhoid Vaccine Acceleration Consortium (TyVAC), a partnership between the Center for Vaccine Development at the University of Maryland School of Medicine, the Oxford Vaccine Group at the University of Oxford, and PATH, an international nonprofit, is committed to ensuring that prevention and control of typhoid is a global health priority. We work with local and global partners to accelerate the introduction of TCVs in LMICs as part of an integrated prevention strategy.

2. We need research and development to advance the typhoid vaccine, drug, and diagnostics pipeline to prevent, accurately diagnose, and treat typhoid.

One of the challenges of typhoid is that an infected person presents with symptoms that are often mistaken for other diseases, which leads to frequent misdiagnoses. Current diagnostics require blood or bone marrow and a lab to analyze the results, which is not feasible for many low-resource health facilities. Knowing that a patient has confirmed typhoid allows the physician to provide the proper course of treatment and helps combat antibiotic misuse.

A robust vaccine and drug pipeline will help ensure that we continue to have a range of prevention and treatment tools at our disposal for typhoid. There are currently several TCVs in various stages of development. New vaccines provide a mechanism for protection against typhoid that can avert cases that may be drug resistant. As more vaccines and drugs become available, access improves and costs can come down due to healthy market competition.

The time is now for us to #TakeonTyphoid. We cannot afford to risk typhoid becoming untreatable—not when we can strengthen prevention through immunization with TCVs and improvements in WASH.

Categories: Guest post, Vaccines

About the author

Dr. Kathleen NeuzilUniversity of Maryland School of Medicine

Dr. Kathleen Neuzil is a professor at the University of Maryland School of Medicine.

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Research Roundup: Dengue diagnostics, unlocking protein structures, and an antibiotic found in soil

Written by Taylor Capizola / GHTC
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In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Brazilian researchers have created a low-cost biosensor product capable of detecting proteins in the membranes of cells infected with dengue, providing a diagnosis in just a few minutes. During its initial testing process, the tool was able to confirm the presence of dengue in all contaminated blood samples tested. While this is a positive start, more testing needs to be done to ensure the tool is continuously reliable in diagnosing dengue and explore options to reduce the price further. If the device proves to be both inexpensive and reliable down the road, it could be a revolutionary tool for diagnosing dengue around the world. In a research lab in Seattle, Washington, Gary Buchko and his team are studying the foundation of the world’s most infectious diseases: proteins. The team is responsible for some of the most groundbreaking work in this niche area of science and have recently identified their 1,000th protein structure responsible for infectious diseases in humans. With the size of a protein being one ten-thousandth the width of a human hair, the work they do is tedious and complex and could take months or years to unlock one single protein structure. But it’s revealing critical information to help design molecules to disrupt or disable the process of these pathogens, paving the way for new vaccines, treatments, and other solutions A compound in Italian soil has been found to have impressive antibiotic properties. The compound, pseudouridimycin (PUM), mimics an RNA building block and is capable of blocking specific polymerase, or enzymes capable of transcribing DNA into RNA. This is important because it can block bacterial polymerase–bacterial enzymes that can make you sick–but it leaves human polymerase intact, allowing PUM to be a highly specific antibiotic tool. Because of this ability as well as the unique structure of the compound, PUM is ten times less likely to trigger a resistance. While this compound has only been tested on animals, results have been promising, and scientists are hoping to advance to human trials within the next three years.
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Research Roundup: Malaria and bone density, a fatal vaccine error, and a sponsored Chikungunya trial

Written by Taylor Capizola / GHTC
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In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. A study recently published in Science Immunology found that mice infected with malaria had shorter thigh bones than their control counterparts by ten percent, suggesting if the same effect takes place in human, children could suffer stunted growth due to malaria infection. Researchers found the malaria parasite left behind waste which killed the mice’s bones, resulting in the disruption of cells responsible for breaking down and rebuilding bones. The researchers found a possible solution, however. By giving the mice a derivative of vitamin D, they were able to stimulate more bone regrowth and suppress the breakdown of bone. Fifteen children have died in a rural South Sudanese village after one needle was used over the course of multiple days with a vaccine that was not stored properly. Almost 50 individuals fell ill after being inoculated on the same day, resulting in 15 deaths due to either sepsis or a related toxicity. According to the World Health Organization (WHO), the series of events were a result of a lack of training and qualification from the individual administering the vaccines, who failed to adhere to WHO immunization safety standards. South Sudan has been affected by a years-long civil war which has reduced the ability to carry out health care services. Immunization coverage has fallen from 77 percent before the conflict down to 44 percent.  The National Institute of Allergy and Infectious Diseases and the National Institutes of Health have sponsored a phase 1-2 Chikungunya vaccine trial at three different sites around the United States, including Emory University, Baylor College of Medicine, and the University of Iowa in Iowa City. The study will focus on three groups, one receiving a high-dose vaccine, one receiving a low-dose vaccine, and a control group. The results will help establish the best dosage and timing for the vaccine. If this trial is successful, the vaccine could become an important tool to combat the Chikungunya endemic in Eastern Africa and prevent the spread of cases within the United States.