Reuters

CDC

Nnadi C, Damisa E, Esapa L, et al. Continued Endemic Wild Poliovirus Transmission in Security-Compromised Areas — Nigeria, 2016. MMWR Morb Mortal Wkly Rep 2017;66:190–193. DOI: http://dx.doi.org/10.15585/mmwr.mm6607a2.

NY Times

• Two million tons of rubble have been cleared
• Two-thirds of the 160,000 damaged homes have been rebuilt
• Half of the 11,000 homes that were destroyed have been rebuilt
• Roads are better, travel faster.
• The first real mall, with a food court and 12 escalators
• Unemployment is high, especially among the many young people graduating from college.
• 50,000 people remain displaced.
• Electricity and water supplies are still near crisis levels.
• Tunnel building goes on

NIH

Tuesday, February 21, 2017

Experimental PfSPZ malaria vaccine provides durable protection against multiple strains in NIH clinical trial

An investigational malaria vaccine has protected a small number of healthy U.S. adults from infection with a malaria strain different from that contained in the vaccine, according to a study published today in the Proceedings of the National Academy of Sciences (PNAS). The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, sponsored and co-conducted the Phase 1 clinical trial.

Malaria is transmitted to humans through the bite of infected mosquitoes, which inject immature malaria parasites called sporozoites into a person’s bloodstream. The parasites travel to the liver, where they mature, multiply and spread via the bloodstream throughout the body causing malaria symptoms including chills, fever, headache, nausea, sweating and fatigue. According to the World Health Organization, 214 million people were infected with malaria globally in 2015 and 438,000 people died, mostly young African children. The species Plasmodium falciparum is the most common cause of malaria morbidity and mortality in Africa. In the United States, travel-related malaria is a concern for international tourists, aid workers and military personnel worldwide.

The PfSPZ Vaccine used in this study was developed by Sanaria Inc., of Rockville, Maryland. The vaccine contains weakened P. falciparum sporozoites that do not cause infection but are able to generate a protective immune response against live malaria infection. Earlier research at the NIH Clinical Center with the PfSPZ Vaccine found it to be safe, well-tolerated and protective for more than a year when tested in healthy U.S. adults against a single Africa-derived malaria strain matched to the PfSPZ Vaccine.

“An effective malaria vaccine will need to protect people living in endemic areas against multiple strains of the mosquito-borne disease,” said NIAID Director Anthony S. Fauci, M.D. “These new findings showing cross-protection with the PfSPZ Vaccine suggest that it may be able to accomplish this goal.”

The study enrolled 31 healthy adults ages 18 to 45 years, and was led by Julie E. Ledgerwood, D.O. of NIAID’s Vaccine Research Center (VRC), and Kirsten E. Lyke, M.D. of the University of Maryland Center for Vaccine Development in Baltimore. Participants were assigned to receive three doses of the PfSPZ Vaccine at eight-week intervals by rapid intravenous injection.

Nineteen weeks after receiving the final dose of the test vaccine, participants who received the vaccine and a group of non-vaccinated volunteers were exposed in a controlled setting to bites from mosquitoes infected with the same strain of P. falciparum parasites (NF54, from Africa) that were used to manufacture PfSPZ Vaccine.

Nine of the 14 participants (64 percent) who received PfSPZ Vaccine demonstrated no evidence of malaria parasites; all six of the non-vaccinated participants who were challenged at the same time had malaria parasites in their blood.

Of the nine participants who showed no evidence of malaria, six participants were again exposed in a controlled setting to mosquito bites, this time from mosquitoes infected with a different strain of P. falciparum parasite, 33 weeks after the final immunization. In this group, 5 of the 6 participants (83 percent) were protected against malaria infection; none of the six participants who did not receive the vaccine and were challenged were protected. All participants who became infected with malaria immediately received medical treatment.

“Achieving durable protection against a malaria strain different from the vaccine strain, over eight months after vaccination, is an indication of this vaccine’s potential,” said Robert A. Seder, M.D., chief of the Cellular Immunology Section of NIAID’s Vaccine Research Center and senior author of the PNAS paper. “If we can build on these findings with the PfSPZ Vaccine and induce higher efficacy, we may be on our way to a vaccine that could effectively protect people against a variety of malaria parasites where the disease is prevalent.”

The research team found that the PfSPZ Vaccine activated T cells, a key component of the body’s defenses against malaria, and induced antibody responses in all vaccine recipients. Vaccine-specific T-cell responses were comparable when measured against both of the malaria challenge strains, providing some insights into how the vaccine was mediating protection.

Ongoing research will determine whether protective efficacy can be improved by changes to the PfSPZ Vaccine dose and number of immunizations.  Accordingly, a Phase 2 efficacy trial testing three different dosages in a three-dose vaccine regimen is now underway in 5-to 12-month-old infants in Western Kenya to assess safety and efficacy against natural infection.

Sanaria Inc., designed, manufactured, and provided PfSPZ Vaccine and the heterologous challenge mosquitoes. NIAID supported the development of the experimental vaccine through several Small Business Innovation Research grants: 5R44AI055229-11, 5R44AI058499-08, and 5R44AI058375-08. For more information about the Phase 1 study, see clinicaltrials.gov using the identifier: NCT02015091.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

WHO

Cholera monthly report for Yemen

NIAID

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has launched a Phase 1 clinical trial to test an investigational vaccine intended to provide broad protection against a range of mosquito-transmitted diseases, such as Zika, malaria, West Nile fever and dengue fever, and to hinder the ability of mosquitoes to transmit such infections. The study, which is being conducted at the NIH Clinical Center in Bethesda, Maryland, will examine the experimental vaccine’s safety and ability to generate an immune response.

The investigational vaccine, called AGS-v, was developed by the London-based pharmaceutical company SEEK, which has since formed a joint venture with hVIVO in London. The consulting group Halloran has provided regulatory advice to both companies.

Unlike other vaccines targeting specific mosquito-borne diseases, the AGS-v candidate is designed to trigger an immune response to mosquito saliva rather than to a specific virus or parasite carried by mosquitoes. The test vaccine contains four synthetic proteins from mosquito salivary glands. The proteins are designed to induce antibodies in a vaccinated individual and to cause a modified allergic response that can prevent infection when a person is bitten by a disease-carrying mosquito.

“Mosquitoes cause more human disease and death than any other animal,” said NIAID Director Anthony S. Fauci, M.D. “A single vaccine capable of protecting against the scourge of mosquito-borne diseases is a novel concept that, if proven successful, would be a monumental public health advance.”

Led by Matthew J. Memoli, M.D., director of the Clinical Studies Unit in NIAID’s Laboratory of Infectious Diseases, the clinical trial is expected to enroll up to 60 healthy adults ages 18 to 50 years. Participants will be randomly assigned to receive one of three vaccine regimens. The first group will receive two injections of the AGS-v vaccine, 21 days apart. The second group will receive two injections of AGS-v combined with an adjuvant, 21 days apart. The adjuvant is an oil and water mixture commonly added to vaccines to enhance immune responses. The third group will receive two placebo injections of sterile water 21 days apart. Neither the study investigators nor the participants will know who is assigned to each group.

Participants will be asked to return to the clinic twice between vaccinations and twice after the second vaccination to undergo a physical exam and to provide blood samples. Study investigators will examine the blood samples to measure levels of antibodies triggered by vaccination.

Each participant also will return to the Clinical Center approximately 21 days after completing the vaccination schedule to undergo a controlled exposure to biting mosquitoes. The mosquitoes will not be carrying viruses or parasites, so the participants are not at risk of becoming infected with a mosquito-borne disease. Five to 10 female Aedes aegypti mosquitoes from the insectary in NIAID’s Laboratory of Malaria and Vector Research will be put in a feeding device that will be placed on each participant’s arm for 20 minutes. The mosquitoes will bite the participants’ arms through the netting on the feeding devices.

Afterward, investigators will take blood samples from each participant at various time points to see if participants experience a modified response to the mosquito bites as a result of AGS-v vaccination.

Investigators also will examine the mosquitoes after the feeding to assess any changes to their life cycle. Scientists suspect that the mosquitoes who take a blood meal from ASG-v-vaccinated participants may have altered behavior that could lead to early death or a reduced ability to reproduce. This would indicate that the experimental vaccine could also hinder disease transmission by controlling the mosquito population.

All participants will be asked to return to the clinic for follow-up visits every 60 days for five months following the mosquito feeding. A final clinic visit to assess long-term safety will take place approximately 10 months after the mosquito feeding. Throughout the trial, an independent Data and Safety Monitoring Board will review study data to evaluate participant safety and the overall conduct of the study. A medical monitor from NIAID’s Office of Clinical Research Policy and Regulatory Operations will also perform routine safety assessments.

The study is expected to be completed by summer 2018. For more information about the trial, see ClinicalTrials.gov using the trial identifier NCT03055000 (link is external).

WHO

National polio immunization campaign launched in Yemen

FluTrackers

FluTrackers

National Health Commission on Strengthening the Medical Treatment of H7N9 Avian Influenza:  “early detection, early reporting, early diagnosis, early treatment”

Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients’ needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected patients.

DNDI

DNDi is working on the following diseases:

• Leishmaniasis
• Sleeping Sickness (human African trypanosomiasis)
• Chagas disease
• Paediatric HIV
• Filarial diseases
• Mycetoma
• Hepatitis C

In 2015, DNDi handed over its Malaria portfolio.

Achievements

Working in partnership with private industry, public institutions, academia and NGOs, DNDi has built the largest ever R&D portfolio for kinetoplastid diseases.

To date, DNDi has successfully delivered, recommended and implemented:

• Two new fixed-dose combinations for Malaria (2007 & 2008) – ASAQ, ASMQ 
• Better simpler treatment against Sleeping Sickness (2009) – NECT
• Cheaper more effective treatment in Africa against Visceral Leishmaniasis (VL) (2010) – SSG&PM
• A set of treatments in South Asia for VL (2011)
• A paediatric form of benznidazole for Chagas disease (2011)
• More effective treatment for children who are co-infected with HIV and TB (2016) – Superbooster Therapy

ISID

High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea

DOI: http://dx.doi.org/10.1016/j.ijid.2017.02.008

Objectives

To explore the epidemiological and clinical factors predictive of the case fatality rate (CFR) of Middle East respiratory syndrome-coronavirus (MERS-CoV) infection in an outbreak in Daejeon, the Republic of Korea.

Methods

We reviewed the outbreak investigation reports and medical records of 1 index case and 25 additional MERS cases in hospitals A (14 cases) and B (11 cases), and conducted an in-depth interview with the index case.

Results

The CFR in hospital B was higher than that in hospital A (63.6% vs. 28.6%, respectively). Higher MERS-CoV exposure conditions were also found in hospital B, including aggravated pneumonia in the index case and nebulizer use in a six-bed admission room. The host factors associated with high CFR were pre-existing pneumonia, smoking history, an incubation period of less than 5 days, leukocytosis, abnormal renal function at diagnosis, and respiratory symptoms such as sputum and dyspnea.

Conclusions

The conditions surrounding MERS-CoV exposure and the underlying poor pulmonary function due to a smoking history or pre-existing pneumonia may explain the high CFR in hospital B. The clinical features described above may enable prediction of the prognosis of MERS cases.