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See the German-language version of this piece at Spektrum zithromax equivalent der Wissenschaft.Jell-O, salad dressings, puddings, jams and jellies, marshmallows, tofu, cream cheese, low-fat hot zithromax online uk dogs. They all have it. And in fact, without it, they would not look or taste like they do. It alters the solid-state physics of these zithromax online uk foods.

It is a gelling agent. But what is a gel, really?. And how does it give these distinctive zithromax online uk foodsâand even some laxatives, pill coatings and cosmeticsâtheir distinct gelness?. A gel is known as a âviscoelasticâ substance.

Physically, it lives somewhere between liquid and solid. Gels are fundamentally composed of polymersâlong zithromax online uk chains of repeating molecules. Gelling agents used in food consist of either protein- or sugar-based polymers. They come from a variety of natural sources, including animals and plant parts.

To get a gel from any of these sources, you need something to change zithromax online uk. Gelation happens when a change in temperature, pressure, pH or concentrationâor when the presence of salts or enzymesâspontaneously releases collagen or cellulose from the tissue to which it is bound. Boiling is often involved, which allows the soup of liberated polymers to come together in a tight embrace. They form a network of surprising complexityâspanning the gamut from linear zithromax online uk strands to branching networks to spherical, glasslike structures.

But gelling agents introduce some stunning functional properties to the foods they help create. Gels can thicken. They can zithromax online uk stabilize. They can control crystal growth of ice and sugar in the food.

They can impart stickiness to liquids. They can make foods elastic or brittle, longer or spreadable, chewy or creamy. They can zithromax online uk substitute for fat. This versatility has been recognized by humans for thousands of years.

One of the first gelling agents to be widely used was isinglass, or âfish glue.â It is derived from the swim bladders of fish and was used by the ancient Romans and medieval bookmakers. Isinglassâs popularity was zithromax online uk only eclipsed with the rise of industrial livestock production. Slaughterhouse remains became the main source of gelatin around the world. An increasing number of people consider gelling agents from animals to be distasteful or unacceptable.

At the zithromax online uk same time, there is growing interest in vegetarian, vegan, halal and kosher products. Luckily, gelling agents abound in the ocean. An example is agar-agar. It is a vegetable gelling agent obtained from the cell walls of red zithromax online uk algae, and it is used in dishes such as flourless noodles, hot apple jelly and Roquefort ice cream.

But there are still other plant-based gels. The next time you pick up a can of soup, a jar of jam or a pack of candies, pay attention to the following additives. Other plant-based gels are:Pectin zithromax online uk. A soluble fiber found in virtually all plants.Carrageenan.

An extract from red seaweed.Cellulose. The main substance zithromax online uk in the walls of plant cells. But despite their history and wide use, some gelling agents may not agree with everyone. For example, carrageenan and agar-agar have caused allergic reactions in some and abdominal cramps or diarrhea in others.

In the European Union, carrageenan is even banned in infant formula as a zithromax online uk precautionary measure. No similar ban exists in the U.S. That is all the more reason to understand if a gelling agent has made its way onto your plate. And thatâs your âServing of Science.â.

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Credit https://www.kentnagano.com/event/hamburgische-staatsorchester-molto-agitato/ zithromax buy cheap. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form zithromax buy cheap of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb.

Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar zithromax buy cheap after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was zithromax buy cheap compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition.

In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of what do you need to buy zithromax uterine fibroids zithromax buy cheap in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. ÂThe cause of the link between the two conditions remains zithromax buy cheap unclear,â she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of zithromax buy cheap scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition. The other authors zithromax buy cheap on this paper were Ginette A.

Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College..

Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb. Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries.

During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition. In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls.

Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. ÂThe cause of the link between the two conditions remains unclear,â she says. However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition.

The other authors on this paper were Ginette A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College..

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Early polling locations in the Hudson Valley and on Long Island can be found here. Dutchess CountyRhinebeck Town Hall - 80 East Market Street, Rhinebeck;Millbrook Fire House - 20 Front Street, Millbrook;DC Board of Elections - 47 Cannon Street, Poughkeepsie;Boardman Road Library - 141 Boardman Rd, Poughkeepsie;Fishkill Town Hall - 807 Route 52, Fishkill.Nassau CountyElmont Public Library - 700 Hempstead Turnpike, Elmont;Floral Park Recreation Center - 124 Stewart St., Floral Park;Freeport Recreation Center - 130 E. Merrick Road, Freeport;Garden City Rec.

Complex St Paulâs Field House - 295 Stewart Ave., Garden City;Hempstead Brierley Park - 65 Dartmouth St., Hempstead;Hicksville Levittown Hall - 201 Levittown Parkway, Hicksville;Lawrence Country Club - 101 Causeway, Lawrence;Massapequa Town Hall South - 977 Hicksville Road, Massapequa;North Merrick Public Library - 1691 Meadowbrook Road, Merrick;Plainview Mid-Island Y JCC - 45 Manetto Hill Road, Plainview;Roslyn Heights Gayle Community Center - 53 Orchard St., Roslyn;Wantagh American Legion Post 1273 - 3484 Park Ave., WantaghWest Hempstead Library - 500 Hempstead Ave., West Hempstead;Westbury Yes We Can Center-New Cassel - 141 Garden St., Westbury;Nassau County Board of Elections - 240 Old Country Road, MineolaOrange CountyCornwall Ambulance Building - 1 Clinton St, Cornwall;Warwick Town Hall - 132 Kings HWY, Warwick;Middletown Senior Center - 62-70 W Main St, Middletown;Village of Montgomery Senior Center - 36 Bridge St, Montgomery;Delaware Engine Company - 22 Hammond St., Port Jervis;Monroe Town Hall - 1465 Orange Tpke., Monroe.Putnam CountyPutnam County Board of Elections - 25 Old Route 6, Carmel.Rockland CountyClarkstown Town Hall - 10 Maple Avenue, New City;Haverstraw Town Hall - 1 Rosman Road, Garnerville;Orangetown Town Hall - 26 West Orangeburg Road, Orangeburg;Ramapo Town Hall - 237 Route 59, Suffern.Suffolk CountyBabylon Town Hall Annex - 281 Phelps Lane, North Babylon;Brookhaven Town Hall - 1 Independence Hill, Farmingville;Dix Hills Fire Department - 115 E Deer Park Road, Dix Hills;Huntington Public Library (Station Branch) - 1335 New York Avenue, Huntington Station;Islip Town Hall Annex - 401 Main Street, Islip;Knights of Columbus - 96 2nd Avenue, Brentwood;Mastic Recreation Community Center - 15 Herkimer Street, Mastic;Nesconset Elementary School - 29 Gibbs Pond Road, Nesconset;Riverhead Senior Center - 60 Shade Tree Lane, Aquebogue;Southold Senior Center - 750 Pacific Street, Mattituck;Stony Brook University Southampton Campus - 70 Tuckahoe Road, Southampton;Windmill Village - 219 Accabonac Road, East Hampton.Sullivan CountySullivan County Government Center - 100 North St., Monticello.Ulster CountyWoodstock Community Center - 56 Rock City Road, Woodstock;Midtown Neighborhood Center - 467 Broadway, Kingston;New Paltz Community Center - 3 Veterans Drive, New Paltz;Highland American Legion - 84 Grand St., Highland;Ellenville Public Library Community Room - 40 Center St., Ellenville.Westchester CountyEastchester Public Library - 11 Oakridge Place, Eastchester;Dobbs Ferry Village Hall - 112 Main Street, Dobbs Ferry;Greenburgh Town Hall - 177 Hillside Ave., White Plains;Veterans Memorial Building - 210 Halstead Ave., Harrison;Pound Ridge Town House - 179 Westchester Ave., Pound Ridge;Mamaroneck Town Center - 740 W. Boston Post Road, Mamaroneck;Mt. Kisco Memorial Complex at Leonard Park - 1 Wallace Drive, Mt.

Kisco;Mount Pleasant Community Center - 125 Lozza Drive, Valhalla;Mount Vernon City Hall - 1 Roosevelt Square, Mount Vernon;New Rochelle City Hall Annex â 90 Beaufort Place, New Rochelle;Joseph G. Caputo Community Center - 95 Broadway, Ossining;Peekskill Nutrition Center â Neighborhood Center - 4 Nelson Ave., Peekskill;Somers Town House - 335 Route 202, Somers;Westchester County Board of Elections - 25 Quarropas St., White Plains;Grinton I. Will Library - 1500 Central Park Ave., Yonkers;Riverfront Library - One Larkin Center, Yonkers;Yorktown Cultural Center - 1974 Commerce St., Yorktown Heights.

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With a record number of people expected to head to the polls next month on zithromax online uk Election Day, New Yorkers can get a jump start and vote early beginning this weekend.Early voting in New York begins on Saturday, Oct. 24, allowing any registered voter to vote at certain sites within their own county zithromax online uk. Early voting lasts zithromax online uk through Sunday, Nov. 1.Voters that may have requested or turned in an absentee ballot can still vote in zithromax online uk person in New York, with the in-person vote being the only one that counts. Anyone who votes zithromax online uk early cannot vote on Election Day on Tuesday, Nov.

3. Early polling locations in the Hudson Valley and on Long Island can be found here. Dutchess CountyRhinebeck Town Hall - 80 East Market Street, Rhinebeck;Millbrook Fire House - 20 Front Street, Millbrook;DC Board of Elections - 47 Cannon Street, Poughkeepsie;Boardman Road Library - 141 Boardman Rd, Poughkeepsie;Fishkill Town Hall - 807 Route 52, Fishkill.Nassau CountyElmont Public Library - 700 Hempstead Turnpike, Elmont;Floral Park Recreation Center - 124 Stewart St., Floral Park;Freeport Recreation Center - 130 E. Merrick Road, Freeport;Garden City Rec. Complex St Paulâs Field House - 295 Stewart Ave., Garden City;Hempstead Brierley Park - 65 Dartmouth St., Hempstead;Hicksville Levittown Hall - 201 Levittown Parkway, Hicksville;Lawrence Country Club - 101 Causeway, Lawrence;Massapequa Town Hall South - 977 Hicksville Road, Massapequa;North Merrick Public Library - 1691 Meadowbrook Road, Merrick;Plainview Mid-Island Y JCC - 45 Manetto Hill Road, Plainview;Roslyn Heights Gayle Community Center - 53 Orchard St., Roslyn;Wantagh American Legion Post 1273 - 3484 Park Ave., WantaghWest Hempstead Library - 500 Hempstead Ave., West Hempstead;Westbury Yes We Can Center-New Cassel - 141 Garden St., Westbury;Nassau County Board of Elections - 240 Old Country Road, MineolaOrange CountyCornwall Ambulance Building - 1 Clinton St, Cornwall;Warwick Town Hall - 132 Kings HWY, Warwick;Middletown Senior Center - 62-70 W Main St, Middletown;Village of Montgomery Senior Center - 36 Bridge St, Montgomery;Delaware Engine Company - 22 Hammond St., Port Jervis;Monroe Town Hall - 1465 Orange Tpke., Monroe.Putnam CountyPutnam County Board of Elections - 25 Old Route 6, Carmel.Rockland CountyClarkstown Town Hall - 10 Maple Avenue, New City;Haverstraw Town Hall - 1 Rosman Road, Garnerville;Orangetown Town Hall - 26 West Orangeburg Road, Orangeburg;Ramapo Town Hall - 237 Route 59, Suffern.Suffolk CountyBabylon Town Hall Annex - 281 Phelps Lane, North Babylon;Brookhaven Town Hall - 1 Independence Hill, Farmingville;Dix Hills Fire Department - 115 E Deer Park Road, Dix Hills;Huntington Public Library (Station Branch) - 1335 New York Avenue, Huntington Station;Islip Town Hall Annex - 401 Main Street, Islip;Knights of Columbus - 96 2nd Avenue, Brentwood;Mastic Recreation Community Center - 15 Herkimer Street, Mastic;Nesconset Elementary School - 29 Gibbs Pond Road, Nesconset;Riverhead Senior Center - 60 Shade Tree Lane, Aquebogue;Southold Senior Center - 750 Pacific Street, Mattituck;Stony Brook University Southampton Campus - 70 Tuckahoe Road, Southampton;Windmill Village - 219 Accabonac Road, East Hampton.Sullivan CountySullivan County Government Center - 100 North St., Monticello.Ulster CountyWoodstock Community Center - 56 Rock City Road, Woodstock;Midtown Neighborhood Center - 467 Broadway, Kingston;New Paltz Community Center - 3 Veterans Drive, New Paltz;Highland American Legion - 84 Grand St., Highland;Ellenville Public Library Community Room - 40 Center St., Ellenville.Westchester CountyEastchester Public Library - 11 Oakridge Place, Eastchester;Dobbs Ferry Village Hall - 112 Main Street, Dobbs Ferry;Greenburgh Town Hall - 177 Hillside Ave., White Plains;Veterans Memorial Building - 210 Halstead Ave., Harrison;Pound Ridge Town House - 179 Westchester Ave., Pound Ridge;Mamaroneck Town Center - 740 W.

Boston Post Road, Mamaroneck;Mt. Kisco Memorial Complex at Leonard Park - 1 Wallace Drive, Mt. Kisco;Mount Pleasant Community Center - 125 Lozza Drive, Valhalla;Mount Vernon City Hall - 1 Roosevelt Square, Mount Vernon;New Rochelle City Hall Annex â 90 Beaufort Place, New Rochelle;Joseph G. Caputo Community Center - 95 Broadway, Ossining;Peekskill Nutrition Center â Neighborhood Center - 4 Nelson Ave., Peekskill;Somers Town House - 335 Route 202, Somers;Westchester County Board of Elections - 25 Quarropas St., White Plains;Grinton I. Will Library - 1500 Central Park Ave., Yonkers;Riverfront Library - One Larkin Center, Yonkers;Yorktown Cultural Center - 1974 Commerce St., Yorktown Heights.

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Aquatic zithromax

A broadly where can i buy zithromax capsules neutralising antibody to prevent HIV transmissionTwo HIV prevention trials (HVTN 704/HPTN 085 aquatic zithromax. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related aquatic zithromax to VRC01 were uncommon.

In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of zithromaxes circulating in the trial regions). However, VRC01 aquatic zithromax did not prevent with other HIV isolates and overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al.

Two randomized trials of neutralizing antibodies to prevent HIV-1 aquatic zithromax acquisition. N Engl J Med. 2021;384:1003â1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 aquatic zithromax who did not.

Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of aquatic zithromax interferonâgamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual aquatic zithromax HIV transmission in men who have sex with men. Clin Infect Dis. 2020;71:2655â2662.The challenge aquatic zithromax of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated to live with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy.

An estimate of the global proportion eligible for treatment was not previously available. A systematic aquatic zithromax review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B zithromax DNA >2000âor >20â000âIU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis.

However, the estimate should be interpreted with caution due to incomplete data acquisition and reporting in aquatic zithromax available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al. Estimating the proportion of people with chronic hepatitis B zithromax eligible for hepatitis B aquatic zithromax antiviral treatment worldwide.

A systematic review and meta-analysis. Lancet Gastroenterol aquatic zithromax Hepatol, 2021. 6:106â119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236â127 women with HIV.

HIV markedly increased the risk aquatic zithromax of cervical cancer (pooled relative risk 6.07. 95%âCI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although the population-attributable fraction for HIV varied geographically, reaching 21% aquatic zithromax (95% CI 15.6% to 26.8%) in the African region.

Cervical cancer is preventable and treatable. Efforts are aquatic zithromax needed to expand access to HPV vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al.

Estimates of the global burden of cervical aquatic zithromax cancer associated with HIV. Lancet Glob Health. 2020.

9:e161â69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma zithromax Most cervical high-risk human papilloma zithromax (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al.

Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women. J Infect Dis 2020. Online ahead of printPublished in STIâthe editorâs choice.

One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal). Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7â15) between tests.

Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556â561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI).

The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women. A recent meta-analysis of over 37â000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15â24âyear-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited.

The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia. Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017.

Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16â35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150âmg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A.

Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle. Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1âmonth after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up.

Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion.

Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex zithromax type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders.

Study site and age were retained in the final model. Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit.

Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1). Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit.

Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1). Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up.

Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods. During the first 6âmonths, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups.

Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25â35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C).

Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively). Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95%âCI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95%âCI (0.81 to 1.04)).

Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95%âCI (0.72 to 0.95)). Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2).

Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95%âCI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95%âCI (0.93 to 1.49)).

And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm. Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group.

The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B). Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms.

Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance.

These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis. Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes.

Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10â12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge.

More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment. Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups.

Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant. However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini.

While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic.

Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

A broadly where can i buy zithromax capsules neutralising antibody to prevent HIV transmissionTwo HIV prevention trials (HVTN 704/HPTN zithromax online uk 085. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related to VRC01 were zithromax online uk uncommon. In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of zithromaxes circulating in the trial regions).

However, VRC01 did not prevent with other HIV isolates and zithromax online uk overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing antibodies to prevent zithromax online uk HIV-1 acquisition. N Engl J Med.

2021;384:1003â1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel zithromax online uk of 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 who did not. Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in zithromax online uk blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferonâgamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network zithromax online uk and sexual HIV transmission in men who have sex with men. Clin Infect Dis. 2020;71:2655â2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 zithromax online uk million people are estimated to live with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy. An estimate of the global proportion eligible for treatment was not previously available.

A systematic review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B zithromax DNA >2000âor >20â000âIU/mL, hepatitis B e-antigen, and overall eligibility for zithromax online uk treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis. However, the estimate should be interpreted zithromax online uk with caution due to incomplete data acquisition and reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al.

Estimating the zithromax online uk proportion of people with chronic hepatitis B zithromax eligible for hepatitis B antiviral treatment worldwide. A systematic review and meta-analysis. Lancet Gastroenterol zithromax online uk Hepatol, 2021. 6:106â119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236â127 women with HIV.

HIV markedly increased the risk of cervical cancer (pooled relative risk zithromax online uk 6.07. 95%âCI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although the population-attributable fraction for zithromax online uk HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region. Cervical cancer is preventable and treatable.

Efforts are needed to expand access to HPV zithromax online uk vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV zithromax online uk. Lancet Glob Health.

2020. 9:e161â69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma zithromax Most cervical high-risk human papilloma zithromax (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

J Infect Dis 2020. Online ahead of printPublished in STIâthe editorâs choice. One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal).

Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7â15) between tests. Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556â561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI). The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women.

A recent meta-analysis of over 37â000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15â24âyear-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited. The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia.

Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017. Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16â35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1âmonth after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up. Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits.

Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion. Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex zithromax type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit. Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1).

Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit. Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device. LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1).

Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up. Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods.

During the first 6âmonths, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups. Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25â35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95%âCI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95%âCI (0.81 to 1.04)). Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95%âCI (0.72 to 0.95)).

Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2). Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95%âCI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95%âCI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95%âCI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ. And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm.

Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group. The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B).

Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms. Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance. These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis.

Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes. Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10â12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups. Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant.

However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini. While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method. It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively.

Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic. Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..