Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.

An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 × 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.

Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA)-48 from Perirectal Swabs.

We evaluated the clinical performance of Check-Direct CPE for carbapenemase detection directly from 301 perirectal swabs (258 patients) in a nonoutbreak setting. Culture of a PCR-confirmed, carbapenemase-containing organism, or history of colonization with such organism within the previous 2 weeks, was used as the reference standard. Check-Direct CPE demonstrated a sensitivity value, specificity value, positive predictive value (PPV), and negative predictive value (NPV) of 100% (all bla(KPC)), 88%, 21%, and 100%, respectively. False positives accounted for 79% (n = 34) of samples for which a cycle threshold (C(T)) value was reached. Simulated studies to evaluate specimen pooling as an approach to minimize costs showed no difference in C(T) values for pooled groups of three or five that each contained a single specimen spiked with ∼1,500 CFU bla(KPC) Klebsiella pneumoniae; however, the detection rate dropped to 60% at a seeded concentration of ∼150 CFU. When data were pooled, C(T) values for bla(KPC) were higher for heavy-feces-containing than for light-feces-containing liquid-suspended specimens. Furthermore, C(T) values for liquid-suspended specimens were 4 to 5 C(T) values lower (i.e., represented greater sensitivity) than those seen in direct swab analysis. Culture was equivalent to or better than Check-Direct CPE for 13/15 (87%) isolates tested in a limit-of-detection analysis. Detection of a carbapenemase gene at a C(T) cutoff value of ≤35 was culture confirmed in 23/24 (96%) of cases; however, C(T) values of >35 overlapped broadly between culture-positive (n = 21) and culture-negative (n = 36) specimens. Check-Direct CPE will likely prove most useful in high-prevalence areas or in outbreak settings where rapid carbapenemase detection is critical for infection control management.

Human herpesvirus 6-A, 6-B, and 7 in vitreous fluid samples.

Human herpesvirus 6 and 7 (HHV-6, HHV-7) have been associated with several neurologic syndromes and have been detected in nervous tissue from healthy persons; however, only two cases of HHV-6A have been reported to be associated with intraocular inflammatory disease. Vitreous fluid was tested from 101 patients, including 69 samples from patients with ocular inflammation including CMV retinitis, idiopathic retinitis, iritis, and vitritis, for HHV-6A, HHV-6B, and HHV-7 DNA by PCR. HHV-6A DNA (4,950 copies per ml) was detected in vitreous fluid from one patient with CMV retinitis, HHV-6B DNA (10,140 copies per ml) was detected in vitreous fluid from one patient with idiopathic ocular inflammation in the absence of CMV DNA, and HHV-7 was not detected in any of the vitreous samples. HHV-6A, HHV-6B, and HHV-7 DNA are detectable in less than 2% of vitreous samples in patients with ocular inflammation.