The “ART” of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban,South Africa

Background

Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa.

Methodology/Principal Findings

We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived ≥10 kilometers from the testing center (RR = 1.37; 95% CI: 1.11–1.71), had a history of tuberculosis treatment (RR = 1.26; 95% CI: 1.00–1.58), or were referred for testing by a health care provider rather than self-referred (RR = 1.61; 95% CI: 1.22–2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors.

Conclusions/Significance

Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.     

Altered olfactory receptor neuron responsiveness in rare Ostrinia nubilalis males attracted to the O. furnacalis pheromone blend

Three percent of E-strain Ostrinia nubilalis males fly upwind in response to the Ostrinia furnacalis pheromone blend [a 40:60 ratio of (E)-12-tetradecenyl acetate to (Z)-12-tetradecenyl acetate (E12-14:OAc to Z12-14:OAc)], in addition to their own pheromone blend [a 99:1 ratio of (E)-11-tetradecenyl acetate to (Z)-11-tetradecenyl acetate) (E11-14:OAc to Z11-14:OAc)]. We assessed the olfactory receptor neuron (ORN) responses of these behaviorally "rare" males versus those of normal males. For the three ORNs housed within each sensillum, we tested responsiveness to Z12-14:OAc, E12-14:OAc, Z11-14:OAc, E11-14:OAc, and the behavioral antagonist (Z)-9-tetradecenyl acetate (Z9-14:OAc). Z11-14:OAc, E11-14:OAc, and Z9-14:OAc stimulated ORNs exhibiting distinct small, large, and medium spike sizes, respectively. For rare and normal males, both Z12-14:OAc and E12-14:OAc usually elicited responses from the largest-spiking ORN. In many ORNs of normal males, Z12-14:OAc or E12-14:OAc stimulated the smaller-spiking ORN that is responsive to Z11-14:OAc. In rare males, detectable ORN responses from the smaller-spiking ORN in response to Z12- and E12-14:OAc were virtually non-existent. These differences in ORN tuning in rare males will tend to create an ORN firing ratio between the large- and small-spiking ORNs in response to the O. furnacalis blend that is similar to that elicited by the O. nubilalis blend.     

Evidence of olfactory antagonistic imposition as a facilitator of evolutionary shifts in pheromone blend usage in Ostrinia spp. (Lepidoptera: Crambidae)

Olfactory receptor neuron (ORN) response was measured to assess why some males ("rare males") of the Asian corn borer (ACB), Ostrinia furnacalis, have a broad behavioral response to fly upwind to both the ACB and the European corn borer (ECB), Ostrinia nubilalis, pheromone blends. We performed single-sensillum electrophysiological recordings on ACB males that had been behaviorally assessed for upwind flight response to the ACB blend [60:40 (Z)-12-tetradecenyl acetate (Z12-14:OAc) to (E)-12-tetradecenyl acetate (E12-14:OAc)], as well as to ECB (Z-strain) and ECB (E-strain) blends [3:97 and 99:1 (Z)-11-tetradecenyl acetate (Z11-14:OAc) to (E)-11-tetradecenyl acetate (E11-14:OAc)]. Sensilla from all types of males had large- and small-spike-sized ORNs responding strongly to Z12- or E12-14:OAc, but weakly to Z11- and E11-14:OAc. In the majority of males ("normal males") that flew upwind only to the ACB blend, Z11-14:OAc elicited responses in an intermediate spike-sized ORN associated with behavioral antagonism that is mainly tuned to (Z)-9-tetradecenyl acetate (Z9-14:OAc). In the rare-type ACB males that flew to both the ACB and ECB pheromone blends, Z11-14:OAc did not stimulate this ORN. Increased responsiveness to ancestral pheromone components by ORNs associated with behavioral antagonism could be instrumental in reproductive character displacement, or in reinforcement and reproductive isolation during speciation by helping to increase assortative mating between males and females in derived populations that use novel sex pheromone blends.     

Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia

We report a sporadic case of chronic progressive external ophthalmoplegia associated with ragged red fibers. The patient presented with enlarged mitochondria with deranged internal architecture and crystalline inclusions. Biochemical studies showed reduced activities of complex I, III and IV in skeletal muscle. Molecular genetic analysis of all mitochondrial tRNAs revealed a G to A transition at nt 4308; the G is a highly conserved nucleotide that participates in a GC base-pair in the T-stem of mammalian mitochondrial tRNA(Ile). The mutation was detected at a high level (approx. 50%) in muscle but not in blood. The mutation co-segregated with the phenotype, as the mutation was absent from blood and muscle in the patient's healthy mother. Functional characterization of the mutation revealed a six-fold reduced rate of tRNA(Ile) precursor 3' end maturation in vitro by tRNAse Z. Furthermore, the mutated tRNA(Ile) displays local structural differences from wild-type. These results suggest that structural perturbations reduce efficiency of tRNA(Ile) precursor 3' end processing and contribute to the molecular pathomechanism of this mutation.     

Evaluation of herbivore-induced plant volatiles for monitoring green lacewings in Washington apple orchards

We evaluated five herbivore-induced plant volatiles plus a male-produced pheromone as attractants for adult green lacewings in Washington apple orchards in 2008. We found at least five attractants or combinations of attractants were attractive to the three most abundant green lacewing species in our trials. Chrysopa nigricornis and Chrysopa oculata were attracted to the combination of methyl salicylate and iridodial with iridodial alone being the second best attractant. Chrysoperla plorabunda was found in lower numbers than C. nigricornis and C. oculata, but did exhibit a significant attraction to benzaldehyde. In mid-summer, we added the herbivore-induced plant volatile squalene to the study and found it to be exceedingly attractive, but only to male C. nigricornis. Whether alone or in combination, squalene attracted 4–5-fold more C. nigricornis than any other compound tested. Our data have revealed C. nigricornis to be an abundant orchard predator that can be readily monitored with squalene-baited traps. Despite the obvious promise of HIPVs in biological control programs, we urge caution in their deployment as large-scale attractants, at least until further studies have investigated potential disruption of natural enemy population dynamics.     

Instar-specific phenology of Pandemis pyrusana and Choristoneura rosaceana (Lepidoptera: Tortricidae) in Washington apple orchards

Head capsule width was used to determine the instar specific phenology of the leafroller Pandemis pyrusana Kearfott and the obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), attacking apple in Washington state during 2001-2003. In total, 7012 P. pyrusana and 6122 obliquebanded leafroller larvae were measured from apple orchards from mid-March to mid-September. Degree-day accumulations from each site were paired with the head capsule data to determine the periods during which different instars were present in the field. The implications of this work for pest management and biological control of leafrollers is discussed.     

Homology of olfactory receptor neuron response characteristics inferred from hybrids between Asian and European corn borer moths (Lepidoptera: Crambidae)

First generation hybrid males from crosses between the Asian corn borer (ACB), Ostrinia furnacalis, and the “univoltine Z-strain” European corn borer (ECB), Ostrinia nubilalis, were examined with respect to behavioral and physiological responses to ACB and ECB pheromones. The hybrid males often flew to the pheromone of ECB Z-strain, but very rarely to the ACB pheromone. We mapped the tuning profiles of each ORN of the F₁ hybrids with respect to the relevant pheromone components and a common behavioral antagonist by employing differential cross-adaptation and varying doses of the ligands. In the trichoid sensilla of F₁ hybrid males, the three co-compartmentalized ORNs produced spikes that were very difficult to distinguish by size, unlike the parental populations. Comparing the responses to ACB and ECB components at different doses reveals overlapping profiles similar to males of both parental types, but more responsiveness to the ECB pheromone components. We were unable to detect any differences in the ORN tuning profiles when comparing males with different behavioral phenotypes. While the two ECB pheromone races have similar ORN tuning properties that are different from those in ACB, the spike-amplitude patterns of ECB E-strain and ACB have greater homology when compared to ECB Z-strain.     

Microbial control of black cutworm (Lepidoptera: Noctuidae) in turfgrass using Agrotis ipsilon multiple nucleopolyhedrovirus

Agrotis ipsilon multiple nucleopolyhedrovirus (family Baculoviridae, genus Nucleopolyhedrovirus, AgipMNPV), a naturally occurring baculovirus, was found infecting black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), on central Kentucky golf courses. Laboratory, greenhouse, and field studies investigated the potential of AgipMNPV for managing black cutworms in turfgrass. The virus was highly active against first instars (LC50 = 73 occlusion bodies [OBs] per microl with 2-microl dose; 95% confidence intervals, 55-98). First instars that ingested a high lethal dose stopped feeding and died in 3-6 d as early second instars, whereas lethally infected fourth instars continued to feed and grow for 4-9 d until death. Sublethal doses consumed by third or fifth instars had little or no effect on subsequent developmental rate or pupal weight. Horizontal transmission of AgipMNPV in turfgrass plots was shown. Sprayed suspensions of AgipMNPV (5 x 10(8) - 6 x 10(9) OBs/m2) resulted in 75 to > 93% lethal infection of third or fourth instars in field plots of fairway-height creeping bentgrass, Agrostis stolonifera (Huds.), and on a golf course putting green collar. Virus spray residues (7 x 10(9) OBs/m2) allowed to weather on mowed and irrigated creeping bentgrass field plots significantly increased lethal infection of implanted larvae for at least 4 wk. This study, the first to evaluate a virus against a pest in turfgrass, suggests that AgipMNPV has potential as a preventive bioinsecticide targeting early instar black cutworms. Establishing a virus reservoir in the thatch and soil could suppress successive generations of that key pest on golf courses and sport fields.