• The Missouri Department of Health and Senior Services yesterday announced a lab-confirmed case of Naegleria fowleri infection in an adult Missouri resident. The single-cell free-living ameba, which thrives in warm freshwater lakes, rivers, and ponds, causes a rare but deadly brain infection called primary amebic meningoencephalitis (PAM), also known as "brain-eating" infection. The patient is being treated in an intensive care unit. Department officials say the source of exposure is being investigated, but preliminary information indicates the patient may have been waterskiing at the Lake of the Ozarks in the days before becoming ill. The infection occurs when water containing N fowleri enters the body through the nose and travels to the brain. There are fewer than 10 PAM cases a year reported in the United States.
• The Massachusetts Department of Public Health (DPH) is warning residents and visitors about potential exposure to Vibrio bacteria in coastal waters. The warning comes after identification of an extremely rare case of Vibrio vulnificus infection likely acquired from exposure to coastal water in Buzzards Bay in southeastern Massachusetts. DPH officials say there have been 71 confirmed and probable infections caused by Vibrio species in Massachusetts this year, and 30% have reported hospitalization. Vibrio bacteria typically cause wound infections and gastrointestinal illness. "People with open wounds who spend time in the water, or those who consume contaminated shellfish, can develop an infection when the bacteria enter the body," DPH Commissioner Robbie Goldstein, MD, PhD, said in a news release. "Sometimes these infections can spread through the bloodstream and cause severe, even life-threatening illness."
• A Legionnaires disease outbreak in Central Harlem has grown to 92 cases, according to the latest update from the New York City Health Department (NYC Health). Department officials say they have sampled and tested water from cooling towers in the investigation zone, and that any cooling tower with initial positive results for Legionella bacteria have completed the treatment required by the department. "We are continuing to monitor and let buildings know if additional treatment is needed," NYC Health said. Fifteen of the confirmed case-patients are currently hospitalized, and three have died. Legionella can cause flu-like symptoms when inhaled.

A study conducted in Zanzibar and mainland Tanzania found evidence that partial resistance to a critical component of malaria treatment is spreading regionally, an international team of researchers reported yesterday in the Journal of Infectious Diseases.

Artemisinin combination therapies (ACTs) are the most effective and widely used treatment for malaria caused by the Plasmodium falciparum parasite and have greatly contributed to global reductions in malaria deaths and complications. While artemisinin partial resistance (ART-R) is widespread in the Greater Mekong Subregion of Southeast Asia, it has recently appeared in Rwanda, Ethiopia, Tanzania, and Uganda, and experts fear it could have a devastating impact if it spreads across Africa, where 95% of malaria cases and deaths are reported.

In the study, a team lead by researchers from the University of North Carolina sequenced 5,202 samples collected from malaria cases in Zanzibar, a semi-autonomous archipelago off the coast of Tanzania, and mainland Tanzania from May 2022 through January 2024. They were looking for mutations in the P falciparum kelch13 (K13) gene that have been connected to ART-R, which can delay parasite clearance and lead to poor treatment outcomes.

"A concern is that ART-R will set the stage for partner drug resistance to emerge in Africa, as more parasites will be exposed to partner drug monotherapy as a part of artemisinin combination therapies," the study authors wrote.

Further spread could threaten ACT efficacy

Of the 1,400 samples sequenced from Zanzibar, 2 contained K13 mutations, while 6 of 3,762 samples from mainland Tanzania contained K13 mutations. Comparison with other malaria genomes from Africa revealed the K13 mutations were distinct from those in Asia, appear to have originated in Africa, and have spread from Tanzania to Zanzibar.

"The emergence of ART-R is concerning for the longevity of ACTs in Africa," the authors wrote. "To date, efficacy generally remains high despite the presence of K13 mutations. However, continued importation and further spread of these resistance mutations could threaten ACT efficacy in Zanzibar."

The authors add that ongoing molecular surveillance to track K13 and other mutations will provide the best early warning sign for potential ACT failure.

Results of a phase 1 randomized controlled trial show that the novel live attenuated type 1 and 3 oral polio vaccines (nOPV1 and nOPV3) have a favorable safety profile and produce a comparable immune response and viral-shedding profile as the homotypic monovalent (single-strain) Sabin-strain oral vaccines (mOPVs).

For the study, published yesterday in The Lancet Infectious Diseases, a team led by PATH and including vaccine maker PT Bio Farma block-randomized 205 adults at four US centers, stratified by site and polio vaccination history (inactivated poliovirus vaccine [IPV] only or regimens including OPV) from May 2021 to February 2023. 

Participants were randomly assigned to receive at least one dose of nOPV or mOPV. IPV participants received one dose of nOPV1 or mOPV1 (cohort 1) or nOPV3 or mOPV3 (cohort 3), and OPV participants received two doses of nOPV1 or mOPV1 (cohort 2) or nOPV3 or mOPV3 (cohort 4) 28 days apart. 

To reduce the seeding of type 2 circulating Sabin-strain circulating vaccine-derived polioviruses (VDPVs), a more genetically stable novel type 2 oral poliovirus vaccine (nOPV2) was deployed in 2021, with surveillance data showing promising safety and efficacy.

Most adverse events mild

Most adverse events were mild, severe events were rare, and solicited events were distributed evenly across groups. Three severe unsolicited adverse events were reported in one mOPV1 and two nOPV1 recipients. 

The safety and immunogenicity evidence generated for nOPV1 and nOPV3 in this phase 1 clinical study were sufficient to justify the now ongoing phase 2 studies in geographically relevant target populations of previously vaccinated children and infants, as well as vaccine-naive neonates.

Homotypic seroprotection was 100% 28 days after the first dose, similar to that of nOPV (86% to 100%) and mPOV (86% to 93%). Fecal viral-shedding rates were comparable among nOPV and mOPV participants.

nOPVs can support the Global Polio Eradication Initiative's Polio Endgame Strategy by providing vaccines less likely to be tied to vaccine-associated paralytic polio and seeding of new circulating VDPVs, the researchers said.

"The safety and immunogenicity evidence generated for nOPV1 and nOPV3 in this phase 1 clinical study were sufficient to justify the now ongoing phase 2 studies in geographically relevant target populations of previously vaccinated children and infants, as well as vaccine-naive neonates," they wrote.