Costs and outcomes of routine HIV oral pre-exposure prophylaxis implementation across different service delivery models and key populations in South Africa.

Background: Oral pre-exposure prophylaxis (PrEP) is a highly efficacious biomedical HIV prevention tool, yet despite being recommended by the World Health Organization (WHO) since 2015, uptake and persistence remain limited in much of the world, including sub Saharan Africa (SSA). There is a dearth of evidence-based interventions to improve PrEP uptake and persistence in SSA, and the full costs of PrEP programs implemented in routine care settings remain largely unknown. This study aimed to evaluate the cost of delivery of daily oral PrEP, and associated outcomes, to different key and priority populations across different service delivery models (SDMs) in South Africa. Methods: We conducted bottom-up micro-costing of PrEP service delivery from the provider perspective within twelve urban SDMs providing routine PrEP services to various key and propriety populations in Gauteng and KwaZulu-Natal provinces in South Africa. The SDMs included in-facility and outreach models that focused on men who have sex with men (MSM), female sex workers (FSW) and adolescent girls and young women (AGYW). We identified all within- and above-facility activities supporting PrEP delivery, obtained input costs from program budgets, expenditure records and staff interviews, and determined individual resource usage between February 2019 and February 2020 through retrospective medical record review. Our primary outcome was PrEP coverage at six months (defined as having sufficient PrEP drug dispensed at the last visit to be covered at six months post PrEP-initiation). A subset (N=633) of all enrolled subjects had the potential for 12 months of follow-up and were included in a 12-month outcome analysis. We report the cost per client initiated on PrEP in 2021 United States Dollars (USD). Findings: We collected medical record data from 1,281 people who initiated PrEP at 12 SDMs between February and August 2019 and had at least six months of potential follow-up. The average number of visits was 2.3 for in-facility models and 1.5 for outreach models and 3,086 months of PrEP was dispensed. PrEP coverage at six months varied greatly across SDMs, from 41.8% at one MSM-focused fixed clinic to 0% in an MSM-focused outreach model. In general, in-facility programs had higher six-month coverage than outreach programs. Across all SDMs with PrEP clients with potential for 12 months of follow-up (n=633), PrEP coverage at 12 months was 13.6%, with variability between SDMs. The average six-month cost per client initiated on PrEP ranged from $29 to $590, with higher average costs generally observed for the in-facility programs ($152 in-facility versus $84 for outreach). The average monthly cost per PrEP client who had six-month PrEP coverage ranged from $18 to $160 dependent on SDM. Interpretation: This study is an important addition to the PrEP outcome and cost literature in the SSA region. Results show that costs and outcomes vary considerably across different SDMs and populations in real world PrEP programs and provide crucial information for further scale-up of the oral PrEP program in South Africa and the greater SSA region.

High levels of PFOS in eggs of three bird species in the neighbourhood of a fluoro-chemical plant.

We studied perfluorooctane sulfonate (PFOS) levels in the eggs of three primarily invertivorous bird species sampled in 2006 near a fluoro-chemical plant: the great tit (Parus major), the northern lapwing (Vanellus vanellus) and the Mediterranean gull (Larus melanocephalus). Our study reported some of the highest PFOS levels ever measured in wildlife to date (i.e. up to 46182ng/g ww in lapwing eggs). A pronounced decrease in PFOS concentration in the Northern lapwing eggs with distance from the fluoro-chemical plant was found. A similar relationship was found for the great tit, with eggs being collected close to the fluoro-chemical plant having significantly higher PFOS levels than eggs collected 1700m further away. When comparing the PFOS levels in eggs for the three species, collected between 1700 and 5500m no significant differences were observed. In addition, when comparing PFOS levels in eggs between Northern lapwing and great tits closer to the plant (900-1700m) no significant differences were found neither. Despite the high levels found in great tit eggs, plasmatic biochemical biomarker responses did not appear to be affected.

Accumulation and maternal transfer of perfluorooctane sulphonic acid in yellow-legged (Larus michahellis) and Audouin's gull (Larus audouinii) from the Ebro Delta Natural Park.

This study aimed to determine the accumulation and maternal transfer of perfluorooctane sulphonic acid (PFOS) in yellow-legged gulls (YLG, Larus michahellis) and the protected species Audouin's gull (AG, Larus audouinii), which cohabit in the Ebro Delta Natural Park (Catalonia, Spain). The Estimated Daily Intake (EDI) through diet (fish and crayfish), depuration rates and transfer capacity from blood to first eggs was studied for a set of 44 pairs. For AG, mean (±SD) EDI was of 128 ± 36 ng/d in males and 119 ± 32 ng/d in females, and for YLG, 170 ± 48 ng/d in males and 159 ± 42 ng/d in females. PFOS levels in blood were higher in males than females (60.6 ± 21 and 61.1 ± 2 7ng/g ww in AG and YLG males versus 25.2 ± 12 and 27.3 ± 14 ng/g ww in AG and YLG females), with little differences among species. The lower levels in females were attributed to the annual release of PFOS to eggs during the laying period, which was estimated of 5544 ± 1571 ng/egg for AG females and 6716 ± 2689 ng/egg for YLG. The overall mass balance of PFOS calculated for both species clearly demonstrates that uptake is higher than elimination rates, considering depuration rates and transfer of PFOS to eggs, and this explains that PFOS is accumulated in gulls in a yearly basis.

Distribution of perfluorinated compounds in Yellow-legged gull eggs (Larus michahellis) from the Iberian Peninsula.

This study is aimed to evaluate the presence and distribution of Perfluorinated Compounds (PFCs) in Yellow-legged gull eggs (Larus michahellis) collected from 8 National or Natural Parks from the Iberian Peninsula. In each colony, 12 eggs were randomly collected and pooled from 3 areas of the colony and analyzed using liquid-solid extraction and liquid chromatography coupled to tandem mass spectrometry. Perfluorooctanate sulfonate (PFOS) was the only compound detected in the eggs and its presence was higher in the colonies situated in NE Iberian Peninsula due to the more industrial and mass urbanization in this area compared to the SW Mediterranean or Atlantic colonies. Accordingly, the Medes site, followed by the Ebro Delta and Columbretes, all situated in the NW Mediterranean coast, contained the highest PFOS levels (40.5-54.0ng/g-ww). In all other colonies, PFOS was detected at levels of 10.1-18.6ng/g-ww. Egg shell biometry was studied and it was found that the presence of PFOS did not affect the development of the egg.

Impact of a perfluorinated organic compound PFOS on the terrestrial pollinator Bombus terrestris (Insecta, Hymenoptera).

Perfluorinated organic chemicals like perfluorooctane sulfonic acid (PFOS) are persistent environmental pollutants that have been measured in a great diversity of wildlife worldwide, especially in the aquatic compartment. However, little information is available on the presence and effects of PFOS in the terrestrial compartment. Therefore, we investigated in this project the risks for effects, bioaccumulation and potential mechanisms of activity of PFOS in the bumblebee Bombus terrestris L. (Hymenoptera: Apidae) that is an important worldwide pollinator in the terrestrial compartment of wildflowers and cultivated crops. The exposure to PFOS occurred orally via the drinking of treated sugar water in a wide range from 1 µg/l up to 10 mg/l, containing environmentally relevant as well as high concentrations, and this was done with use of microcolonies of B. terrestris in the laboratory. A chronic toxicity assay demonstrated high bumblebee worker mortality (up to 100%) with an LC(50) of 1.01 mg/l (R(2) = 0.98). In addition, PFOS posed strong detrimental reproductive effects, and these concerted with a dramatic reduction in ovarian size. HPLC-MS demonstrated a bioaccumulation factor of 27.9 for PFOS in bumblebee workers fed with sugar water containing 100 µg/l PFOS during 5 weeks (2184 ± 365 ng/g BW). Finally, potential mechanisms of activity were investigated to explain the significant impact of PFOS on survival and reproduction capacity of B. terrestris. Exposure of bumblebee workers to PFOS resulted in a significant decrease in mitochondrial electron transport activity (p = 0.035) and lipid amounts (p = 0.019), while the respective p-values were 0.58 and 0.12 for protein and glucose amounts. Hence, addition of PFOS to ecdysteroid responsive Drosophila melanogaster S2 cells resulted in a strong antagonistic action on the EcR-b.act.luc reporter construct, demonstrating that PFOS may exert its effects partially through an endocrine disrupting action via the insect molting hormone or ecdysteroid receptor.

Screening of perfluorinated chemicals (PFCs) in various aquatic organisms.

The aim of this study was to evaluate the occurrence of five perfluorinated chemicals (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid) in aquatic organisms dwelling in either freshwater or marine ecosystems. Organisms selected were insect larvae, oysters, zebra mussels, sardines, and crabs, which are widespread in the environment and may represent potential bioindicators of exposure to PFCs. The study comprises the optimization of a solid-liquid extraction method and determination by high-performance liquid chromatography coupled to tandem mass spectrometry. Using spiked zebra mussels at 10 and 100 ng/g level, the method developed provided recoveries of 96% and 122%, and 82% to 116%, respectively, and a limit of detection between 0.07 and 0.22 ng/g ww. The method was highly sensitivity and robust to determine PFC compounds in a wide array of biological matrices, and no matrix interferents nor blank contamination was observed. Among organisms studied, none of the bivalves accumulated PFCs, and contrarily, insect larvae, followed by fish and crabs contained levels ranging from 0.23 to 144 ng/g ww of PFOS, from 0.14 to 4.3 ng/g ww of PFOA, and traces of PFNA and PFHxS. Assessment of the potential use of aquatic organisms for biomonitoring studies is further discussed.

Spatial distribution and sources of perfluorochemicals in the NW Mediterranean coastal waters (Catalonia, Spain).

This study provides the first evidence of the sources and loads of perfluorochemicals (PFCs) to the NW Mediterranean Sea. Five PFCs were analyzed in 45 seawater samples collected along the Catalan coast. Total PFCs ranged from 0.07 to 13.0 ng/l, being the levels higher in ports than in coastal waters. To determine the sources of PFCs, 8 wastewater treatment plants (WWTPs) effluents and 6 rivers discharging to the sea were also analyzed. WWTP effluents contained total PFCs levels ranging from 3.47 to 132 ng/l but due to the relatively low discharge flows, they contributed to 34.7 g/d to the sea. Total PFCs in rivers ranged from 2.24 to 21.9 ng/l and were the principal PFCs contributors to the sea. Overall, a total load of 190 g/d of PFCs are discharged to the NW Mediterranean coast. The effects and risk of PFCs discharges to the Mediterranean basin are discussed.

The relationship between perfluorinated chemical levels in the feathers and livers of birds from different trophic levels.

Although feathers have been used successfully for monitoring heavy metals and organic pollutants, there are currently no data available on the use of feathers as indicators of perfluorinated chemical (PFC) exposure in birds. Also, no study has evaluated PFC levels in birds with different diets from different habitats. In the current study we investigated the PFC exposure of five different bird species from the same geographic region in Belgium, using both feathers and liver tissue. The highest mean liver perfluorooctane sulfonate (PFOS) levels were found in the Grey Heron (476 ng/g ww) followed by the Herring Gull (292 ng/g ww) and Eurasian Sparrowhawk (236 ng/g ww), whereas the Eurasian Magpie (17 ng/g ww) and the Eurasian Collared Dove (12 ng/g ww) had the lowest levels. The PFOS levels in the feathers showed a different pattern. The Grey Heron had the highest feather PFOS levels (247 ng/g dw), the Eurasian Sparrowhawk (102 ng/g dw) had the second highest feather PFOS levels, followed by the Herring Gull (79 ng/g dw) and the Eurasian Collared Dove (48 ng/g dw), and the lowest levels were found in the Eurasian Magpie (31 ng/g dw). Overall, there was a significant positive correlation (Pearson, R=0.622, p<0.01) between the feather and liver PFOS levels, indicating that feathers could be an alternative bioindicator for PFOS exposure in birds. However, caution should be taken as there was no significant correlation between the PFOS levels in the feathers and livers of the individual species. In general, birds from a higher trophic level had higher PFC levels in their tissues. This indicates that diet plays a role in PFC exposure in birds and confirms the bioaccumulation potential of PFC.

Behaviour of damselfly larvae (Enallagma cyathigerum) (Insecta, Odonata) after long-term exposure to PFOS.

Perfluorooctane sulfonic acid (PFOS) is a persistent and ubiquitous environmental contaminant that has been detected in organisms worldwide. Here, we evaluate whether long-term (1 and 4 months) exposure to PFOS contamination affects the behavioural performance of freshwater larvae of the damselfly Enallagma cyathigerum (Insecta: Odonata). Our results show reduced behavioural performance with increasing PFOS concentration. In 1 month exposed larvae, no observed effect concentrations (NOECs) were 100 microg/L for general activity. In 4 months exposed larvae, NOECs were 10 microg/L, for each behavioural trait, except swimming acceleration of male larvae where the NOEC was 100 microg/L. When faced with PFOS concentrations above the NOEC, E. cyathigerum larvae were less active, less capable to escape a simulated predator attack and less efficient in foraging. Together, our results show that damselfly larvae suffer reduced survival-related behavioural performance.

High accumulation of perfluorooctane sulfonate (PFOS) in marine tucuxi dolphins (Sotalia guianensis) from the Brazilian coast.

Perfluorooctane sulfonate (PFOS) and other perfluoroalkyl compounds (PFCs) were measured in liver samples from 29 marine tucuxi dolphins from Rio de Janeiro state (RJ), Brazil. PFC measurement combined liquid chromatography and mass spectrometry, using a CapLC system connected to a Quadrupole-LIT mass spectrometer. PFOS was the only PFC detected and it was so in all samples. PFOS concentrations (ng x g(-1) dw) of dolphins (n=23) from the highly contaminated Guanabara Bay (in RJ) varied between 43 and 2431 as well as between 76 and 427 from areas of RJ other than the quoted bay (n=6). Concentrations of three fetuses and one neonate varied between 664 and 1590. Fetus/mother ratios were calculated in two situations (2.75 and 2.62). It seems that mother-to-calf transference plays important role for relationships between PFOS and age. When a one-year-old male calf presenting 2431 ng x g(-1) dw was excluded from the test, significant correlations were observed between PFOS concentrations and both age and total length. Despite the placental transference, PFOS concentrations were not significantly lower in females than in males. PFOS levels in marine tucuxi dolphins from Guanabara Bay are among the highest detected to date in cetaceans, and this may represent a threat to the small population concerned.