Microbicide & Safe Sex (11)

Pubic Lice

Pubic Lice also called crab lice or "crabs," pubic lice are parasitic insects found primarily in the pubic or genital area of humans. Pubic lice infestation is found worldwide and occurs in all races, ethnic groups, and levels of society.

Pubic lice usually are found in the genital area on pubic hair; but they may occasionally be found on other coarse body hair, such as hair on the legs, armpits, mustache, beard, eyebrows, or eyelashes. Pubic lice on the eyebrows or eyelashes of children may be a sign of sexual exposure or abuse.

Pubic lice have forms: the egg (also called a nit), the nymph, and the adult.

Nit: Nits are lice eggs. They can be hard to see and are found firmly attached to the hair shaft. They are oval and usually yellow to white. Pubic lice nits take about 6-10 days to hatch.

Nymph: The nymph is an immature louse that hatches from the nit (egg). A nymph looks like an adult pubic louse but it is smaller. Pubic lice nymphs take about 2-3 weeks after hatching to mature into adults capable of reproducing. To live, a nymph must feed on blood.

Adult: The adult pubic louse resembles a miniature crab when viewed through a strong magnifying glass. Pubic lice have six legs; their two front legs are very large and look like the pincher claws of a crab. This is how they got the nickname "crabs." Pubic lice are tan to grayish-white in color. Females lay nits and are usually larger than males. To live, lice must feed on blood. If the louse falls off a person, it dies within 1-2 days.

Microbicide &Safe Sex (10)

PID

Pelvic inflammatory disease (PID) is an infection of the female reproductive organs. It usually occurs when sexually transmitted bacteria spread from your vagina to your uterus and upper genital tract. Many women who develop pelvic inflammatory disease either experience no signs or symptoms or don't seek treatment. Pelvic inflammatory disease may be detected only later when you have trouble getting pregnant or if you develop chronic pelvic pain.

Symptoms in PID range from subclinical (asymptomatic) to severe. If there are symptoms, then fever, cervical motion tenderness, lower abdominal pain, new or different discharge, painful intercourse, or irregular menstrual bleeding may be noted. It is important to note that even asymptomatic PID can and does cause serious harm. Laparoscopic identification is helpful in diagnosing tubal disease, 65–90% positive predictive value in patients with presumed PID. Regular Sexually Transmitted Infection (STI) testing is important for prevention. Treatment is usually started empirically because of the serious complications that may result from delayed treatment. Definitive criteria include: histopathologic evidence of endometritis, thickened filled fallopian tubes, or laparoscopic findings. Gram-stain/smear becomes important in identification of rare and possibly more serious organisms.

A woman can get PID if bacteria (germs) move up from her vagina and infect her pelvic organs. Many different types of bacteria can cause PID. But, most cases of PID are caused by bacteria that cause 2 common sexually transmitted infections (STIs) — gonorrhea and chlamydia. It can take from a few days to a few months for an infection to travel up from the vagina to the pelvic organs.

You can get PID without having an STI. Normal bacteria found in the vagina and on the cervix can sometimes cause PID. No one is sure why this happens. You can get pelvic inflammatory disease without having an STI. Normal bacteria found in the vagina and on the cervix can sometimes cause pelvic inflammatory disease. No one is sure why this happens.

(Excerpts of) A Summary of Preclinical Topical Microbicide Vaginal Safety and Chlamydial Efficacy Evaluations in a Pigtailed Macaque Model

Patton, Dorothy L. PhD; Cosgrove Sweeney, Yvonne T. BA; Paul, Kathleen J. MPH

Background:
The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.

Methods:
We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer.

Results:
Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection.

Conclusions:
The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.

Overall safety profiles were acceptable in 24 products. Microbiologic findings common to most products included stable populations of H2O2-producing lactobacilli and Viridans streptococci and transient decreases in anaerobic Gram-negative rods.

Microbicide Safety

The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.


The physico-chemical and biological properties of active pharmaceutical ingredients (APIs) and their formulations are the foundation of safe, efficacious and acceptable microbicides. Hence, the initial selection of the API and its primary formulation is crucial. Certain undesirable properties of an API can be compensated or masked by an appropriate formulation. However, there is a risk in proceeding with inadequate APIs or formulations, as they may fail later in development, costing more time and money. 

It is important to have a set of criteria that inform Go/No Go decisions prior to entering in clinical trials. This set of criteria is based on API and formulation parameters derived from a comprehensive evaluation of their in vitro P/C properties, drug release rates, specific activity, and cell and tissue toxicity, which in turn represent the base for animal studies focused on organ toxicity/safety, pharmacokinetics (PK), and pharmacodynamics (PD) and efficacy.

A solid preclinical foundation will help navigate clinical testing successfully, ultimately leading to a safe and effective microbicide. In addition to the more classical IND-enabling studies, new models, assays and biomarkers have been developed and adapted to the evaluation of genital and rectal microbicides.

Experience with previous microbicide candidates has led to the inclusion of assays evaluating the impact of genital environmental factors such as low pH, seminal plasma, CV secretions and microflora on microbicide safety and efficacy. Microbicide-induced inflammatory mediators and alteration of innate immunity have also been recently incorporated to the standard testing.