Nzambi Khonde

Mycoplasma genitalium: an organism commonly associated with cervicitis among west African sex workers

Objectives: To identify the contribution of Mycoplasma genitalium to the aetiology of cervicitis in sub-Saharan Africa and its relative importance in the overall burden of sexually transmitted infections among female sex workers (FSW). Methods: The study population consisted of FSW recruited in Ghana and Bénin during the initial visit of a randomised controlled trial. A questionnaire was administered, a pelvic examination carried out, and cervical samples obtained for detection of M genitalium, Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Clinical signs potentially indicating cervicitis were cervical discharge, pus on the cervical swab, bleeding after sampling, and inflammatory cervix. Results: Among 826 FSW, 26.3% were infected with M genitalium. N gonorrhoeae was strongly and independently associated with each of the four signs of cervicitis (adjusted odds ratios (AOR): 4.1 to 6.0). The AOR for C trachomatis were intermediate (1.3–4.1) and the AOR for M genitalium were lower (between 1.6 and 1.8) but statistically significant (p⩽0.05) for each sign. Conclusions:M genitalium is weakly associated with signs of cervicitis in west African FSW but is highly prevalent.

In the heart of darkness: sleeping sickness in Zaire

Human African trypanosomiasis (HAT) control programs existed during the colonial era in the Belgian Congo. HAT cases peaked in 1930 at 33,562. They declined gradually to about 1000 cases in 1959. The civil war that erupted after Zaires independence in 1960 crippled the public health system. During 1960-1967, no active case finding was conducted and notification of HAT cases fell greatly. Mismanagement and corruption maintained a severe social and economic crisis after the civil war. At the end of the 1980s, the number of new HAT cases began to increase from the relatively stable numbers of 4000-6000 during 1969-1981 to almost 10,000. Socioeconomic conditions deteriorated quickly in the 1990s. The withdrawal of foreign aid in 1991 devastated many governmental health facilities that had been dependent on these funds. In much of Zaire, Catholic and Protestant missions were the only health care providers. The breakdown of the health system contributed to epidemics of Ebola fever, dysentery, the plague, and cholera. The specialized mobile teams providing trypanocidal drugs to HAT patients could no longer operate, resulting in drug shortages and thousands of deaths. The teams were somewhat remobilized during 1993-1994, when some foreign aid was again available. A return to neglected areas in 1994 found the HAT prevalence to be 15.4/1000 in the Equator region. In Kimbanzi, Bandundu region, it was 718/1000 among 241 persons examined. Had the teams not arrived when they did, the entire village of Kimbanzi could have disappeared within 1-2 years. The high prevalence rates in neglected areas were the highest rates recorded this century. The neglect brought about an increase in the number of infectious people, an increase in transmission, and a higher cost and toxicity of treatment due to an increase in late-stage HAT cases. The estimated true total incidence of HAT in Zaire in 1994 was about 34,400 new cases. The number of HAT deaths in 1994 was probably at least 80 times higher than that of Ebola deaths in 1995. Proper HAT control methods need to be fully funded and implemented to control this curable disease.

Etiology of urethral discharge in West Africa: the role of Mycoplasma genitalium and Trichomonas vaginalis

OBJECTIVE To determine the etiological role of pathogens other than Neisseria gonorrhoeae and Chlamydia trachomatis in urethral discharge in West African men. METHODS Urethral swabs were obtained from 659 male patients presenting with urethral discharge in 72 primary health care facilities in seven West African countries, and in 339 controls presenting for complaints unrelated to the genitourinary tract. Polymerase chain reaction analysis was used to detect the presence of N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum. FINDINGS N. gonorrhoeae, T. vaginalis, C. trachomatis, and M. genitalium--but not U. urealyticum--were found more frequently in men with urethral discharge than in asymptomatic controls, being present in 61.9%, 13.8%, 13.4% and 10.0%, respectively, of cases of urethral discharge. Multiple infections were common. Among patients with gonococcal infection, T. vaginalis was as frequent a coinfection as C. trachomatis. M. genitalium, T. vaginalis, and C. trachomatis caused a similar clinical syndrome to that associated with gonococcal infection, but with a less severe urethral discharge. CONCLUSIONS M. genitalium and T. vaginalis are important etiological agents of urethral discharge in West Africa. The frequent occurrence of multiple infections with any combination of four pathogens strongly supports the syndromic approach. The optimal use of metronidazole in flowcharts for the syndromic management of urethral discharge needs to be explored in therapeutic trials.

Real-Time PCR Quantification of Genital Shedding of Herpes Simplex Virus (HSV) and Human Immunodeficiency Virus (HIV) in Women Coinfected with HSV and HIV

ABSTRACT The accuracy and usefulness of laboratory-developed real-time PCR procedures using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131 primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to detect accurately the majority of HIV-1 subtypes of group M circulating in sub-Saharan Africa, including subtypes A, B, C, D, and G as well as circulating recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the intra- and interassay coefficients of variation of CT values were 1.30% and 0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR for HSV using primers and probe targeting the HSV DNA polymerase gene allowed both detection and quantification of HSV DNA and also differentiation between HSV-1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5 copies per assay; the intra- and interassay coefficients of variation of CT values were 0.96% and 1.49%, respectively. Both manual and automated silica-based procedures were appropriate for combined extraction of HIV and HSV genomes from female genital secretions. Taken together, these findings indicate that real-time PCR may be used as a unique nucleic acid amplification procedure to detect and quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at reduced costs the genital shedding of both viruses in women included in intervention studies.

HIV infection among sex workers in Accra: need to target new recruits entering the trade.

Objective: Description of the epidemiology of HIV infection among sex workers (SW) in Accra, Ghana. Methods: In all, 1013 SW working out of their homes (seaters) or finding customers in bars, hotels, brothels or on the street (roamers) were interviewed and tested for HIV. Results: Overall, prevalence of HIV infection was nearly 50% (506 of 1013), varying from 26% (133 of 507) among the roamers to 74% (368 of 496) among the seaters. Profound differences were noted between these two categories of SW with regard to age, number of clients per day, price per instance of intercourse, condom use, and other characteristics. Respectively, 27% and 58% of roamers and seaters were infected with HIV within their first 6 months of sex work, despite a limited number of unprotected sex acts with seropositive clients. Independent risk factors for HIV infection varied between types of SW: age among the roamers; region of origin and duration of sex work among the seaters; number of clients per day, and presence of current or past genital ulcer and gonococcal cervicitis in both groups. Conclusion: In Accra, considerable heterogeneity exists in the population of SWs. In both categories of SW, new recruits become rapidly infected with HIV after entering the trade. The 25‐fold higher prevalence of HIV among SWs than in the general adult population suggests that in Accra, as in many cities of West Africa, a high fraction of new cases of HIV infection continue to be acquired from SWs. Intervention programs targeting SW should be an essential component of national AIDS control strategies. Special efforts should be made to identify and offer preventive services to new sex workers.

Low prevalence of cervical infections in women with vaginal discharge in west Africa: implications for syndromic management

Objectives: To measure prevalence and risk factors for cervical infections among a large sample of women consulting for vaginal discharge in west Africa and to evaluate its syndromic management through a two visit algorithm. Methods: In 11 health centres in Bénin, Burkina Faso, Ghana, Guinée, and Mali 726 women who presented with a vaginal discharge without abdominal pain and who denied being a sex worker (SW) were enrolled. Cervical samples were tested for the detection of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with polymerase chain reaction (PCR) assays. All participants were treated with single dose (2 g) metronidazole and clotrimazole cream for 3 days. They were randomised to be told either to come back on day 7 only if there was no improvement in the discharge (group A), or to come back on day 7 regardless of response to treatment (group B). Results: Overall, the prevalence of NG and CT was only 1.9% (14/726) and 3.2% (23/726) respectively. Risk factors previously recommended by the WHO were not associated with the presence of cervical infection, with the exception of the number of sex partners in the past 3 months. When taken together, these risk factors had a positive predictive value of only 6.4% to identify cervical infections. Prevalence of cervical infection was not higher in women who came back on day 7, regardless of the strategy used. Prevalence of NG/CT was lower in Ghana and Bénin (5/280, 1.8%), where comprehensive interventions for SW have been ongoing for years, than in the three other countries (27/446, 6.1%, p = 0.01). Conclusions: NG and CT infections are uncommon in west African women who consult for vaginal discharge and who are not SW. Syndromic management of vaginal discharge should focus on the proper management of vaginitis. The control of gonococcal and chlamydial infection should be redesigned around interventions focusing on sex workers.

Epidemiological evidence for immunity following Trypanosoma brucei gambiense sleeping sickness

In order to investigate whether protective immunity appears after Trypanosoma brucei gambiense sleeping sickness, we undertook a retrospective cohort study of 3 remote villages in central Zaire (total population 1431), in which 38% of all adults had a past history of human African trypanosomiasis. Among adults previously diagnosed with trypanosomiasis and treated, the risk of a second episode of trypanosomiasis during the 10 years period of observation was only 15% (with a 24 months refractory period) and 30% (without a refractory period) of the risk of a first episode in adults never previously diagnosed. We could not demonstrate a similar difference among children, to some extent because only a few of them were diagnosed for a first time with trypanosomiasis. Our findings suggest that very significant immunity appears after Gambian sleeping sickness, and that developing a vaccine against this subspecies of trypanosomes is biologically plausible.

The Complex Vaginal Flora of West African Women with Bacterial Vaginosis

Background The spectrum of bacteria associated with bacterial vaginosis (BV) has recently expanded through taxonomic changes and the use of molecular methods. These methods have yet to be used in large-scale epidemiological studies in Africa where BV is highly prevalent. Methods An analysis of samples obtained during a clinical trial of the management of vaginal discharge in four West African countries. Samples were available from 1555 participants; 843 (54%) had BV. Nucleic acids of 13 bacterial genera or species potentially associated with BV were detected through the polymerase chain reaction. Results The associations between various components of the vaginal flora were complex. Excluding Lactobacillus, the other 12 micro-organisms were all associated with each other at the p≤0.001 level. The prevalence of various bacterial genera or species varied according to age, sexual activity and HIV status. In multivariate analysis, the presence of Gardnerella vaginalis, Bifidobacterium, Megasphaera elsdenii, Dialister, Mycoplasma hominis, Leptotrichia, and Prevotella were independently associated with BV as was the absence of Lactobacillus and Peptoniphilus. However, Mobiluncus, Atopobium vaginae, Anaerococcus, and Eggerthella were not independently associated with BV. Unexpectedly, after treatment with a regimen that included either metronidazole or tinidazole, the proportion of patients with a complete resolution of symptoms by day 14 increased with the number of bacterial genera or species present at enrolment. Conclusions Numerous bacterial genera or species were strongly associated with each other in a pattern that suggested a symbiotic relationship. BV cases with a simpler flora were less likely to respond to treatment. Overall, the vaginal flora of West African women with BV was reminiscent of that of their counterparts in industrialized countries.

The syndromic management of vaginal discharge using single-dose treatments: a randomized controlled trial in West Africa.

OBJECTIVE To evaluate whether single-dose treatments are as effective as standard therapy in the syndromic management of vaginal discharge. METHODS A randomized controlled effectiveness trial compared single-dose tinidazole plus fluconazole (TF) with treatment for 7 days with metronidazole plus 3 days of treatment with vaginal clotrimazole (MC) among 1570 women presenting with vaginal discharge at primary health care institutions in Ghana, Guinea, Mali and Togo. Participants were randomly allocated to one of the two treatments by research nurses or physicians using precoded envelopes. Effectiveness was assessed by symptomatic response on day 14. CLINICAL IDENTIFIER ClinicalTrials.gov NCT00313131. FINDINGS The two treatment regimens had similar effectiveness: complete resolution was seen in 66% (TF) and 64% (MC) and partial resolution in 33% (TF) and 34% (MC) of participants (P = 0.26). Effectiveness was similar among subgroups with vulvovaginal candidiasis, Trichomonas vaginalis vaginitis or bacterial vaginosis. The two treatment regimens had a similar effectiveness among human immunodeficiency virus (HIV)-infected (TF: n = 76, 71% complete resolution, 28% partial; MC: n = 83, 72% complete resolution, 25% partial, P = 0.76) and HIV-uninfected women (TF: n = 517, 68% complete, 32% partial; MC: n = 466, 65% complete, 33% partial, P = 0.20). Cervical infections with Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium were uncommon among women not involved in sex work, were associated with bacterial vaginosis or T. vaginalis vaginitis, and did not alter response to treatment with agents active against vaginal infections. Four-fifths of women not relieved by a single dose of TF had a favourable response when MC was administered as second-line treatment. CONCLUSION Single-dose TF is as effective as multiple-dose MC in the syndromic management of vaginal discharge, even among women with HIV-infection. Given its low price and easier adherence, TF should be considered as a first-line treatment for vaginal discharge syndrome.

Improvement of clinical algorithms for the diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis by the use of Gram-stained smears among female sex workers in Accra, Ghana.

Background: Screening for cervical infection is difficult in developing countries. Screening strategies must be improved for high‐risk women, such as female sex workers. Goal: To evaluate the sensitivity and specificity of screening algorithms for cervical infection pathogens among female sex workers in Accra, Ghana. Study Design: A cross‐sectional study among female sex workers was conducted. Each woman underwent an interview and a clinical examination. Biologic samples were obtained for the diagnosis of HIV, syphilis, bacterial vaginosis, yeast infection, Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis infection. Signs and symptoms associated with cervicitis agents were identified. Algorithms for the diagnosis of cervical infection were tested by computer simulations. Results: The following prevalences were observed: HIV, 76.6%; N gonorrhoeae, 33.7%; C trachomatis, 10.1%; candidiasis, 24.4%; T vaginalis, 31.4%; bacterial vaginosis, 2.3%; serologic syphilis, 4.6%; and genital ulcers on clinical examination, 10.6%. The best performance of algorithms were reached when using a combination of clinical signs and a search for gram‐negative diplococci on cervical smears (sensitivity, 64.4%; specificity, 80.0%). Conclusions: In the algorithms, examination of Gram‐stained genital smears in female sex workers without clinical signs of cervicitis improved sensitivity without altering specificity for the diagnosis of cervical infection.