Kat Kelley

Amid the Zika outbreak and with new vector control approaches in the pipeline, there has been much talk about the feasibility and potential risks and benefits of eradicating mosquitos. National Institute of Allergy and Infectious Diseases (NIAID) Director Dr. Anthony Fauci advocated for mosquito elimination in a recent STAT News article, joking that their only known role in the natural ecosystem is feeding birds. However, Dr. Andrew Dobson, a professor of ecology and evolutionary biology at Princeton University, argues that such an approach would be “naïve and foolish,” noting that there are more than 3,000 mosquito species, hundreds that bite humans, but just three that are responsible for the vast majority of human disease transmission. Further, Dobson suggests that we can’t predict the consequences of mosquito eradication on the natural ecosystem, and that it could lead to the development of insecticide-resistant mosquitos. Meanwhile, NPR asked experts about the feasibility of eradicating even just one mosquito species and the resources required for it to be successful. First, global coordination mechanisms and high-level political will would be required, i.e., through the appointment of a United Nations mosquito czar. Next, financial resources are a must, with Pennsylvania State University Biologist and Entomologist Dr. Andrew Read estimating that US$250-500 million would be required to eliminate the Aedes aegypti mosquito—responsible for transmitting Zika, yellow fever, dengue, and chikungunya—a high pricetag but one that pales in comparison to the $1.5 billion pharmaceutical company Sanofi spent on developing a vaccine against just one of those diseases, dengue fever. With all the resources in place, the czar would then have to determine which vector control approach to take. As pathogens grow resistant to existing insecticides, both new insecticides and mutant mosquito interventions are under development. British biotech company Oxitec is currently testing its sterile-male mosquitos in Brazil. Oxitec’s mosquitos are released into the wild where they mate with female A. aegypti mosquitos, producing offspring that don’t live to adulthood and consequently can’t infect humans. The approach has resulted in an 82 percent decrease in the presence of A. aegypti larvae in the region in just nine months. Another intervention involves releasing mosquitos infected with Wolbachia bacteria, which then spreads among the mosquito population and can reduce the mosquitos’ ability to produce healthy offspring and to transmit viruses to humans. Finally, scientists are developing mosquitos using “gene-drive” technology, which involves releasing mosquitos genetically modified to be unable to lay eggs or transmit diseases. A team of scientists at the University of Texas Medical Branch (UTMB) have created a genetically modified mouse that is susceptible to Zika virus, making it the first animal model that can be used to test drugs and vaccines against the virus. The study, published in The American Journal of Tropical Medicine and Hygiene, provides further evidence that Zika is sexually transmitted and that it impacts the nervous system, as the viral load in mice was highest in the spleen, brain, and testes. The team, led by UTMB Virologist Dr. Shannan Rossi, developed the model in just three weeks, an impressive feat for a process that normally takes several months. UTMB scientists are also using the model to test an antiviral drug, developed for dengue fever, against Zika. The mouse model will be invaluable to scientists, particularly in light of the dearth of research on Zika. However, the mouse amnion—in which fetal development takes place—varies significantly from the human amnion, and thus, scientists are continuing to look for animal models that can shed light on the impact of Zika during pregnancy.

One-third of the world’s population—more than 2 billion people—has latent tuberculosis (TB) and each year, 9.6 million people develop active TB. However, a team of scientists have identified 16 genes, referred to as a “risk signature,” that can predict which cases are most likely to progress to active TB. In two studies enrolling more than 10,000 participants across South Africa and Gambia, researchers collected and analyzed blood samples to detect the presence of the risk signature. The genes predicted cases of active TB with sensitive and specificity rates of 66.1 percent and 80.6 percent: in other words, two-thirds of the patients with the genetic risk signature developed active TB during the study, compared to only one-fifth of those without the risk signature. TB is the world’s leading infectious disease killer, resulting in 1.5 million deaths in 2014. However, the study suggests that this risk signature could be used to predict cases of active TB up to 18 months in advance, and treating latent TB can reduce the risk of developing the disease by 90 percent. A new tool to easily insert intrauterine devices (IUDs)—long-acting contraceptive devices that can remain in the uterus for up to twelve years—could make the devices more accessible in low-resource settings. IUDs contain either copper, which is toxic to sperm, or hormones that preclude the release of eggs from the ovaries. The devices are safe and more than 99 percent effective, however, they can be difficult to insert. However, a new IUD inserter could make the contraceptive devices much more accessible, particularly for postpartum woman. The inserter was developed by Population Services International, in partnership with Stanford Program for International Reproductive Education and Services and Pregna International Ltd., costs just US$1, and is longer and sturdier than existing tools. In a trial enrolling 80 women in India each of whom had given birth just hours before, 90 percent of health workers reported that the IUD was easy to place with the new inserter and more than 90 percent of women felt no increase in pain during the procedure. Improved inserters could have a significant impact in settings without ultrasound technology—used to confirm the placement of the IUD—or with limited ability to sterilize equipment. Next Billion took an in-depth look at existing vaccines to prevent and treat cancer, emphasizing their need in low-resource settings, where cancer testing and treatment are often inaccessible and prohibitively expensive. Rather than targeting pathogens, these vaccines train the immune system to attack cancerous cells. There are currently preventative vaccines available against strains of human papillomavirus (HPV) and hepatitis B virus that cause cervical and liver cancer, respectively, and other vaccines available and under development can prevent the spread or relapse of bladder, prostrate, and lung cancer. Cervical cancer results in more deaths among women in low- and middle-income countries than any other type of cancer. Fortunately, HPV vaccines prevent against several strains of the virus, including the two responsible for 70 percent of cases. Liver cancer ranks second in cancer mortality worldwide, however, many cases could be averted with increased access to hepatitis B vaccines. Individuals infected with hepatitis B are 100 times more likely to develop liver cancer. Lung cancer is the leading cause of death from cancer worldwide, and non-small cell lung cancer (NSCLC) accounts for 85 percent of cases. However, researchers in Cuba are developing a therapeutic vaccine against NSCLC, which has extended survival rates for patients by 68 percent in phase 3 trials. Additionally, the TB vaccine is used to fight bladder cancer and the vaccine Sipuleucel-T is used against advanced prostate cancer.

US Senator Bernie Sanders (I-VT) released a plan last week as part of his Democratic presidential bid to incentivize research and development (R&D) for new HIV and AIDS medicines while ensuring they remain affordable. Under his proposal, drug companies would receive a cash prize for market introduction of a novel HIV and AIDS therapy, but would not receive exclusive marketing rights, an idea he first proposed in 2012. The prize would reflect the “therapeutic value” of the treatment as well as the number of people expected to benefit from the product. To finance these cash prizes, the Senator is proposing a Prize Fund for HIV and AIDS of US$3 billion per year. Eliminating exclusive market rights for these new drugs would ensure that generic products could immediately enter the market, spurring competition and lowering prices. However, critics argue that the proposal could take limited research funding away from other diseases and note that the plan does not detail how the size of the cash award would be determined for a given drug or to whom it would be distributed (i.e., the patent holder, the regulatory sponsor, public-sector agencies involved in the basic research, etc.). Photo: CDC The US Food and Drug Administration (FDA) announced last week its tentative approval of a trial of genetically engineered mosquitos to combat mosquito-borne diseases, pending 30 days of public comment. The mosquitos, developed by British company Oxitec, are intended to reduce the population of Aedes aegypti mosquitos, which transmit the Zika, dengue, chikungunya, and yellow fever viruses. The mosquitos are all male and when they reproduce with native mosquitos, their offspring are not viable, dying before reaching adulthood. The trial, if approved, will take place in the Florida Keys; Oxitec’s mosquitos would be released up to three times per week for up to 22 months. After a careful review, the FDA has determined, in collaboration with the US Centers for Disease Control and Prevention and the Environmental Protection Agency, that the trial is safe for humans, animals, and the environment. The agency noted that the trial will be short and that the Aedes aegypti “occupy a fairly uncontested ecological niche,” making it unlikely that another mosquito population would expand to fill the vacuum. The United Nations Children’s Fund (UNICEF) and the government of Malawi are conducting a pilot program to determine the cost, feasibility, and impact of using drones—unmanned aerial vehicles—to expedite HIV and AIDS testing for infants. In Malawi, 10 percent of adults are HIV-positive, and there are 130,000 children living with HIV and AIDS. However, it can take up to ten weeks to get HIV test results for infants born to mothers with HIV and AIDS, who require specialized testing. The blood samples are transported by ambulance or bike to one of only eight labs in the country capable of conducting these tests. It then takes at least two weeks for the tests to be completed, and often the results wait in the lab until there is a large batch. UNICEF and the Malawi government are testing the feasibility of drone delivery at different times and in different weather conditions and will be comparing the costs, which include electricity for charging the device and the hardware itself, to current delivery methods, which include fuel and driver salaries. The goal is to reduce testing time from more than two months to just a few days, ensuring that children with HIV and AIDS can start treatment much sooner.

A new study out of the Washington University School of Medicine in St. Louis, Missouri, revealed a proliferation of antibiotic-resistant bacteria in the gastrointestinal tracts of premature infants. The team collected fecal samples from 84 babies born premature and identified nearly 800 genes that enable bacteria to develop resistance to 16 different antibiotics. Preterm infants are more susceptible to infection and nearly all are given antibiotics preemptively for at least the first few days of life. However, this practice could have unintended consequences; high bacterial diversity in the gut protects against infection from harmful bacteria, and the study indicated that preterm infants have one-tenth the number of bacteria species found in babies born full term. The team used a novel technique to identify genes that can confer drug resistance, resulting in the discovery of hundreds of genes not previously associated with antibiotic resistance. Further, the findings suggest that administering one antibiotic can result in a growth in resistance to other antibiotics. However, breastfeeding and aging appeared to have a positive impact on the infants’ gut, resulting in increased bacterial diversity. A novel, low-cost technique can diagnose tuberculosis (TB) in 25 minutes using just a urine sample. Standard TB tests require X-rays and/or mucus samples, which are harder to acquire than urine samples, particularly in low-resource settings. In a study of more than 2,500 patients across four countries in sub-Saharan Africa, use of the test reduced TB deaths in HIV and AIDS patients by four percent, as improved detection enabled patients to start treatment early. In Africa alone, 300,000 HIV and AIDS patients die of TB annually, and thus, this diagnostic technique could save thousands of lives each year. The new tool costs US$2.66 per test, whereas the leading TB test costs $10 and requires a $17,000 machine to read the results. Last week, US government representatives met with scientists and public health officials to discuss a White House ban, instated 18 months ago, on research that makes viruses more dangerous than natural strains. Within the scientific community, many argue that such research can be done safely, and that the potential scientific and public health benefits are significant, whereas others contend that the benefits are overstated and the risk is too high. The officials met to discuss the establishment of a high-level committee which would review proposals for such studies, weighing the potential benefits and risks, evaluating the security of the laboratory facilities, and determining whether the results could be achieved through less risky research. Prior to the meeting, Dr. Inglesby—CEO of the UPMC Center for Health Security—along with Drs. Lipsitch and Relman of Harvard University and Stanford University, proposed policy options for conducting such research safely. The recommendations include: requiring a high-level official to approval such research (i.e., the director of the National Institutes of Health), defining “red lines” for research that would prompt additional safety reviews, limiting such research to select labs with the highest level of security, or requiring the purchase of insurance policies for such research.

This International Women’s Day, GHTC is celebrating two novel, female-initiated health technologies that have the potential to give women and girls greater control over their sexual and reproductive health, empowering them to make informed decisions about whether and when to have children and to protect themselves and their families from HIV and other sexually transmitted infections (STIs). The Women’s Condom. Photo: PATH/Glenn Austin This International Women’s Day, GHTC is celebrating two novel, female-initiated health technologies that have the potential to give women and girls greater control over their sexual and reproductive health, empowering them to make informed decisions about whether and when to have children and to protect themselves and their families from HIV and other sexually transmitted infections (STIs). GHTC members PATH and the International Partnership for Microbicides (IPM) both recently announced exciting milestones in developing and expanding access to game-changing contraceptive and HIV/STI prevention tools that help women negotiate safer sex. The Woman’s Condom, manufactured by Shanghai Dahua Medical Apparatus Co., Ltd, (DAHUA) and marketed under various brand names including O’Lavie, received World Health Organization (WHO)/United Nations Population Fund (UNFPA) prequalification last week. This approval opens the door for its purchase and distribution by United Nations (UN) agencies and other leading international organizations for distribution in the public sector. And just the week before, IPM announced the results of two large Phase 3 clinical trials—The Ring Study and ASPIRE—which showed that a monthly vaginal ring containing the antiretroviral drug (ARV) dapivirine, developed by IPM, can safely help protect women from HIV. Enduring unmet need for family planning and HIV/STI prevention methods Globally, an estimated 225 million women have an unmet need for family planning and more than 350 million new cases of curable STIs occur every year. Women's and adolescent girls' contraceptive and HIV/STI prevention needs vary across geographies and cultures and often change throughout a woman’s life. Therefore, unmet need can only be addressed through ensuring access to a range of contraceptive options. When women and adolescent girls make contraceptive decisions, they have a lot to consider: Cost Efficacy Ease of use Side effects, health concerns, and whether a hormonal or non-hormonal option is right for them Ease of access, including how often they’d have to visit a health clinic or pharmacy and the reliability of the supply of in their community Stigma(s) surrounding contraceptive use and whether they can discreetly access contraceptives Comfort and whether the product impacts pleasure during intercourse Whether they can use or administer the contraceptive themselves or must rely on a health worker or partner. Biologically and as a result of gender-based violence and discrimination, women and girls are at greater risk for HIV infection. In sub-Saharan Africa, women aged 15 to 24 are twice as likely to become infected with HIV compared to their male peers. And often, women are not empowered to negotiate safe sex with their partners, particularly the use of male condoms. The prevention methods currently available aren’t doing enough to stop the alarming rates of infection in women in sub-Saharan Africa and are often unrealistic options for them. What makes these tools so game-changing for women? The Woman’s Condom and the dapivirine ring put the power of protection in the hands of women. The Woman’s Condom was developed by PATH, CONRAD, and other partners through a user-centered design process across four countries. “This iterative process enabled the partners to create a product that truly met the needs of women and couples. The Woman’s Condom is easy to insert, use and remove; stays in place during intercourse; and is comfortable, providing good sensation for both partners,” said Patricia Coffey, head of PATH’s Health Technologies for Women and Children Team. “Unlike other female condoms on the market, the Woman’s Condom’s main pouch is compressed into a narrow, rounded capsule which women insert like a tampon. And importantly, women can insert it themselves, without relying on their partner’s cooperation. It provides another option in cases where a male partner won’t use a male condom, and it also enables a woman to bring something to the relationship…it gives the woman a chance to take a more proactive role in protecting herself and her partner,” said Coffey. The dapivirine ring (Photo: International Partnership for Microbicides) The dapivirine ring is the first long-acting HIV prevention method designed for women. It adapts a medical device commonly used to deliver hormones to women—the vaginal ring—to deliver an ARV drug. The ring is easy for a woman to insert and remove herself, can be left in for one month, and used without the knowledge of a sexual partner. In two large Phase 3 clinical trials across four countries in sub-Saharan Africa, the ring was shown to reduce HIV infection rates by 31 and 27 percent overall. This is the first time two Phase 3 studies have confirmed statistically significant efficacy for a microbicide to prevent HIV. The studies found differences in efficacy by age and level of use: For women over 21, who appeared to use the ring more consistently, the ring reduced infection by 37 and 56 percent. The dapivirine ring could “give new hope to many women at high risk who need more and different options to effectively protect themselves from HIV,” according to IPM Founding Chief Executive Officer Dr. Zeda Rosenberg. “We are also hopeful we can learn more about how to help women who want to use the ring do so consistently, which could help increase protection.” What do these announcements mean for access to these innovative new tools? WHO/UNFPA prequalification represents an important step in increasing access to the Woman’s Condom, which is currently approved for use in China, Europe, Malawi, South Africa, and Zambia. Prequalification serves as an endorsement of quality, efficacy, and safety, particularly for nations with limited regulatory capacity. It not only enables UN agencies to procure the Woman’s Condom, but the US Agency for International Development—one of the largest female condom procurers worldwide—could rely on WHO prequalification, when a product has not been reviewed by the US Food and Drug Administration. Introduction of the Woman’s Condom in new countries could also further grow the market for female condoms broadly. Because of its innovative insertion design, the Woman’s Condom has proven popular among users and some have even called the product “elegant” and “beautiful,” according to Coffey. Thus, the Woman’s Condom could help attract new users to the female condom product category and help normalize and increase regular and consistent use of female condoms. The results from the two dapivirine ring trials are a significant step forward to getting an affordable microbicide ring into the hands of women who can benefit from it. Next, IPM will submit the dapivirine ring for regulatory review while simultaneously working with partners and governments to determine how the product can best strengthen HIV prevention efforts. IPM also plans to conduct an open-label extension (OLE) study that would provide former Ring Study participants with access to the dapivirine ring and enable IPM to collect additional information on its safety and efficacy. Such a study could help IPM better understand real-world use of the dapivirine ring, and awareness of the ring’s safety and efficacy could increase adherence among participants, as was seen in follow-up OLEs of oral pre-exposure prophylaxis. The trial results also open the door to next-generation prevention products. IPM has several other microbicide products in the pipeline, including vaginal rings combining dapivirine with other ARVs and a vaginal ring containing dapivirine and a contraceptive hormone, which would last for three months and prevent both unintended pregnancy and HIV. The combination ARV rings are in Phase 1 and preclinical development, and the dapivirine-contraceptive ring is expected to enter a Phase I trial later this year.

Photo: PATH/Map Photo Agency Gilead Sciences, a California-based biopharmaceutical company, has received US Food and Drug Administration (FDA) approval for Odefsey®, a complete, single-pill regimen for HIV and AIDS. Odefsey® contains tenofovir alafenamide (TAF), a modified version of the antiviral tenofovir, used to treat HIV and AIDS and hepatitis B. TAF is highly effective at entering HIV cells, and thus can be administered in doses a mere ten percent of that required for tenofovir-based medicines. Gilead also recently received a positive opinion from the European Medicines Agency (EMA) on Descovy, another TAF-based treatment. The EMA’s recommendation will be evaluated by the European Commission, which can grant regulatory approval for the 28 European Union member states. Prior to the 2014 Ebola outbreak, the experimental therapy ZMapp had only been tested in non-human primates. The therapy, which is comprised of three antibodies against the virus, is particularly difficult to manufacture, and thus only seven patients received ZMapp during the outbreak. Now, results of the first human clinical trial of ZMapp affirms that the treatment could be an important tool in fighting Ebola. The randomized control trial was conducted by the US National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the governments of Guinea, Liberia, and Sierra Leone. As the spread of Ebola slowed, so too did new cases, and thus the partners could only enroll 72 patients, one-third of the 200 for which they had planned. In the study, all patients received supportive care, including provision of fluids and electrolytes, and half of patients received three doses of ZMapp. Patients receiving ZMapp recovered much faster, in terms of symptoms and presence of the virus in the blood, and the fatality rate was lower for ZMapp recipients: 22 versus 37 percent. Despite the small trial size, NIAID Director Dr. Tony Fauci is optimistic that the FDA will “favorably consider” the results, in light of the dearth of approved Ebola treatments and positive animal study results, in which the drug was 100 percent effective. A team of Google engineers is working with the United Nations Children’s Fund (UNICEF) to develop a platform to track and predict the spread of Zika, a mosquito-borne virus linked to birth defects that was recently declared a Public Health Emergency in Latin America. The platform uses data such as weather and travel patterns to anticipate communities at-risk for Zika, and will be adaptable for use in other outbreaks. Google is also providing a US$1 million grant to UNICEF for mosquito control and behavior change efforts, with the goal of reaching 200 million people throughout the Americas. The company is also working to ensure that helpful, accurate information is readily available to all using the search engine, adding detailed information in 16 languages on Zika prevention and symptoms as well as government public health alerts.