Experimental hut evaluation of a novel long-lasting non-pyrethroid durable wall lining for control of pyrethroid-resistant Anopheles gambiae and Anopheles funestus in Tanzania.

BACKGROUND: A novel, insecticide-treated, durable wall lining (ITWL), which mimics indoor residual spraying (IRS), has been developed to provide prolonged vector control when fixed to the inner walls of houses. PermaNet® ITWL is a polypropylene material containing non-pyrethroids (abamectin and fenpyroximate) which migrate gradually to the surface. METHODS: An experimental hut trial was conducted in an area of pyrethroid-resistant Anopheles gambiae s.l. and Anopheles funestus s.s. to compare the efficacy of non-pyrethroid ITWL, long-lasting insecticidal nets (LLIN) (Interceptor®), pyrethroid ITWL (ZeroVector®), and non-pyrethroid ITWL + LLIN. RESULTS: The non-pyrethroid ITWL produced relatively low levels of mortality, between 40-50% for An. funestus and An. gambiae, across all treatments. Against An. funestus, the non-pyrethroid ITWL when used without LLIN produced 47% mortality but this level of mortality was not significantly different to that of the LLIN alone (29%, P = 0.306) or ITWL + LLIN (35%, P = 0.385). Mortality levels for An. gambiae were similar to An. funestus with non-pyrethroid ITWL, producing 43% mortality compared with 26% for the LLIN. Exiting rates from ITWL huts were similar to the control and highest when the LLIN was present. An attempt to restrict mosquito access by covering the eave gap with ITWL (one eave open vs four open) had no effect on numbers entering. The LLIN provided personal protection when added to the ITWL with only 30% blood-fed compared with 69 and 56% (P = 0.001) for ITWL alone. Cone bioassays on ITWL with 30 min exposure after the trial produced mortality of >90% using field An. gambiae. CONCLUSIONS: Despite high mortality in bioassays, the hut trial produced only limited mortality which was attributed to pyrethroid resistance against the pyrethroid ITWL and low efficacy in the non-pyrethroid ITWL. Hut ceilings were left uncovered and may have served as a potential untreated refuge. By analogy to IRS campaigns, which also do not routinely treat ceilings, high community coverage with ITWL may still reduce malaria transmission. Restriction of eave gaps by 75% proved an inadequate barrier to mosquito entry. The findings represent the first 2 months after installation and do not necessarily predict long-term efficacy

The Effectiveness of Non-pyrethroid Insecticide-treated Durable Wall Lining to Control Malaria in Rural Tanzania: Study Protocol for a Two-armed Cluster Randomized Trial.

Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts

Sequential low-dose step-up and step-down protocols with recombinant follicle-stimulating hormone in polycystic ovary syndrome: prospective comparison with step-down protocol.

PURPOSE: To assess the differences in follicular development comparing two sequential low-dose step-up and step-down protocols (A: 37.5 IU/day, B: 75 IU/day) with a step-down protocol (C: 150 IU/day) using recombinant human follicle stimulating hormone (rFSH) in women with polycystic ovarian syndrome (PCOS). METHODS: In this prospective observational comparative study, 60 PCOS women were treated with one of the three protocols for only one cycle. RESULT(S): Monofollicular development was similar among the three protocols but the total number of follicles >10 mm in diameter was significantly lower in group A (1 ± 0.94 vs 6.3 ± 2.45 vs 8.6 ± 4.45; P = 0.001 A vs B; P < 0.001 A vs C). Cycle cancellation rate was higher in protocol A and in protocol C because of no ovarian response and excessive multifollicular development, respectively. The total amount of rFSH for complete cycle was significantly lower in protocol A (P = 0.02 A vs B; P = 0.007 A vs C). No mild or severe hyperstimulation syndrome (OHSS) was observed. CONCLUSION(S): A and B protocols seem to be a more effective approach than the step-down protocol. In both groups, the pregnancy rate for started cycle was the same. Protocol A has allowed the development of a lower number of small follicles, single pregnancies, but an excessive number of cancelled cycles occurred. In protocol B no cycle cancellation occurred, though the total rFSH dosage was significantly higher than the protocol A and two twin pregnancies were observed

Can anti-Müllerian hormone be predictive of spontaneous onset of pregnancy in women with unexplained infertility?

The objective of the study was to assess anti-Müllerian hormone's (AMH) role in predicting spontaneous onset of pregnancy. This observational cohort study included 83 women with unexplained infertility and normal or low ovarian reserve. Serum AMH, FSH, LH, 17β-oestradiol, inhibin B levels were measured and the number of early antral follicles (2-9 mm) was evaluated on days 2-5 of the cycle. Spearman's correlation was used for comparison of strength of correlation. The diagnostic power of AMH in predicting spontaneous pregnancy was evaluated by receiver operating characteristic (ROC) curves. Markers of ovarian reserve in pregnant women and women without pregnancy were similar. In the entire study population, any markers (AMH, FSH, AFC, age), correlated with each other, but no marker was correlated with pregnancy. The area under the ROC curve for AMH reached a value of 0.385 ± 0.07 (0.25-0.52, 95% confidence interval, CI); for FSH 0.415 ± 0.08 (0.25-0.58, 95% CI); for AFC 0.418 ± 0.08 (0.26-0.57, 95% CI), for age 0.496 ± 0.08 (0.34-0.65, 95% CI). The study did not find a predictive role for AMH in predicting spontaneous onset of pregnancy. Even when AMH levels are very low, a spontaneous pregnancy may still occur

Platelet-derived growth factor effects on purified testicular peritubular myoid cells: binding, cytosolic Ca++ increase, mytogenic activity, and extracellular matrix production enhancement

The response of purified rat testicular peritubular myoid cells (PMC) to platelet-derived growth factor (PDGF) was studied. Freshly isolated PMC were devoid of measurable amounts of PDGF-binding sites. However, after 1 day in culture in serum-free conditions, specific high affinity receptors were detected. The estimated binding sites per cell revealed that PMC express more receptors for PDGF-BB, followed by PDGF-AB and PDGF-AA. PDGF treatment of cultured PMC increased the cytosolic Ca2+ concentration, showing a rank order of potencies with PDGF-BB &gt; PDGF-AB &gt; PDGF-AA. PMC proliferation, as measured by direct cell counting, was also stimulated by all three PDGF isoforms, with the same order of potencies observed for the increase in intracellular Ca2+. This effect was inhibited by antibodies to PDGF. Moreover, PDGF treatment increased the release of type IV collagen and fibronectin, and induced the release of type V collagen and laminin. These results demonstrate that testicular PMC are induced to express functionally active PDGF receptors in response to cell culturing. These data suggest that PMC may be a target for PDGF and that PDGF-mediated effects in vivo are dependent on factors regulating the expression of the receptors. The role that PDGF may play in normal and pathological testicular processes is discussed