Sylvie Deslandes

Comparison of the Directigen Flu A+B Test, the QuickVue Influenza Test, and Clinical Case Definition to Viral Culture and Reverse Transcription-PCR for Rapid Diagnosis of Influenza Virus Infection

ABSTRACT The diagnostic performances of the clinical case definition of influenza virus infection based on the combination of fever and cough and of two rapid influenza diagnostic tests, the Directigen Flu A+B test (Directigen; BD Diagnostic Systems, Sparks, Md.) and the QuickVue influenza test (QuickVue; Quidel, San Diego, Calif.), were compared to those of viral culture and an in-house reverse transcription (RT)-PCR during the 2000-2001 flu season. Two hundred consecutive nasopharyngeal aspirates were analyzed from 192 patients, including 122 adults and 70 children. Viral culture identified influenza virus A in 16 samples and influenza virus B in 55 samples, whereas RT-PCR identified influenza virus A in 21 samples and influenza virus B in 64 samples. When RT-PCR was used as the reference standard, the likelihood ratios for a positive test were 40.0 for Directigen, 8.6 for QuickVue, and 1.4 for the combination of fever and cough, whereas the likelihood ratios for a negative test were 0.22, 0.16, and 0.48, respectively. Our study suggests that (i) the poor specificity (35 to 58%) and the poor positive predictive value (41 to 60%) of the clinical case definition of influenza preclude its use for prediction of influenza virus infections during epidemics, especially when infection control decision making in the hospital setting is considered; (ii) Directigen has a higher diagnostic yield than QuickVue but is associated with a larger number of invalid results; (iii) the sensitivities of the rapid diagnostic tests are significantly lower with samples from adults than with samples from children, with the rates of false-negative results reaching up to 29%; and (iv) RT-PCR detects more cases of influenza than viral culture, and this greater accuracy makes it a more useful reference standard.

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.

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.

Mycoplasma genitalium is not associated with adverse outcomes of pregnancy in Guinea-Bissau

Objective: To evaluate the impact of Mycoplasma genitalium on the outcome of pregnancy. Methods: Cervical samples from women who had previously participated in a case-control study (designed to assess the impact of syphilis and HIV-2 on the outcome of pregnancy in Guinea-Bissau) were processed using a PCR assay to detect the presence of M genitalium. Controls were women who had delivered a term neonate with a birth weight over 2500 g. Cases were classified into four groups of mothers according to the outcome of pregnancy: stillbirths, spontaneous abortions, premature deliveries, and small for gestational age (SGA) babies. Results: Among the 1014 women included in this study, 6.2% were infected with M genitalium. M genitalium infection was not significantly associated with any of the adverse outcomes of pregnancy studied. Odds ratios (OR) for premature or SGA delivery in the presence of M genitalium infection were 1.37 (95% CI 0.69 to 2.60) and 0.44 (95% CI 0.01 to 2.75), respectively. For abortions and stillbirths, OR were respectively 0.61 (95% CI 0.07 to 2.51) and 1.07 (95% CI 0.42 to 2.42). Conclusion:M genitalium appears not to have a deleterious impact on the outcome of pregnancy.

Iatrogenic Transmission of Human T Cell Lymphotropic Virus Type 1 and Hepatitis C Virus through Parenteral Treatment and Chemoprophylaxis of Sleeping Sickness in Colonial Equatorial Africa

BACKGROUND The simultaneous emergence of human immunodeficiency virus (HIV)-1 group M and HIV-2 into human populations, circa 1921-1940, is attributed to urbanization and changes in sexual behavior. We hypothesized that the initial dissemination of HIV-1, before sexual transmission predominated, was facilitated by the administration, via reusable syringes and needles, of parenteral drugs against tropical diseases. As proxies for highly lethal HIV-1, we investigated risk factors for hepatitis C virus (HCV) and human T cell lymphotropic virus 1 (HTLV-1) infections, blood-borne viruses compatible with prolonged survival, in an area known in 1936-1950 as the most virulent focus of African trypanosomiasis. METHODS Cross-sectional survey of individuals 55 years and older in Mbimou land and Nola, Central African Republic. Dried blood spots were used for HCV and HTLV-1 serologic testing and nucleic acid detection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were measured by logistic regression. RESULTS The only risk factor for HCV genotype 4 infection was treatment of trypanosomiasis before 1951 (OR, 3.13; 95% CI, 1.38-7.09). HTLV-1 infection was associated with having received 2 injections of pentamidine for trypanosomiasis chemoprophylaxis (adjusted OR, 2.03; 95% CI, 1.01-4.06) and with transfusions (adjusted OR, 2.82; 95% CI, 1.04-7.67). From historical data, we predicted that 59% of Mbimous 65 years and older would report treatment for trypanosomiasis before 1951; only 11% did so. CONCLUSIONS Treatment of trypanosomiasis before 1951 may have caused iatrogenic HCV transmission. Population-wide half-yearly intramuscular pentamidine for trypanosomiasis chemoprophylaxis in 1947-1953 may have caused iatrogenic HTLV-1 transmission. These and other interventions against tropical diseases could have iatrogenically transmitted SIV(cpz), jump-starting the HIV-1 epidemic. The excess mortality among patients with trypanosomiasis treated before 1951 supports this hypothesis.

Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic.

The molecular epidemiology of hepatitis C virus (HCV) in the Central African Republic (CAR) is poorly documented. Thus, we conducted phylogenetic analyses of NS5B gene sequences from 58 HCV-infected inhabitants of a remote area of south-west CAR, which indicated that 48 (82.8%) were infected with genotype 4 (HCV-4), five (8.6%) with genotype 2 and five (8.6%) with genotype 1. HCV-4 strains were highly heterogeneous, containing previously described subtypes 4k (48%), 4c (27%), 4r (4%), 4f (4%) and unclassified subtypes (17%). To estimate the epidemic history of these HCV-4 strains, an evolutionary analysis using the coalescent approach was used. The estimated date of the most recent common ancestor of the CAR HCV-4 strains was 1539 (95% confidence intervals, 1317-1697). They exhibited a rapid, exponential spread from 1935 to 1965, simultaneously with what was recently reported in neighbouring Cameroon and Gabon. The hypothesis of a massive iatrogenic transmission during interventions for the control of endemic tropical diseases is discussed.

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.

Recent H3N2 swine influenza virus with haemagglutinin and nucleoprotein genes similar to 1975 human strains

Of the four pandemic strains of human influenza A virus observed this century, the 1977 virus strain was very similar in all genes to a 1950 isolate. Since mammalian influenza A viruses change annually by genetic drift, this reappearance could only be attributed at that time to conservation of the virus in a frozen state. We report here the isolation of swine influenza A viruses with haemagglutinin and nucleoprotein genes which are virtually identical to those of the human virus that circulated in 1975. We have also found serological evidence that this virus is circulating extensively in Quebec swine herds. We propose that human-like H3N2 influenza A strains may remain invariant for long periods in swine, which may serve as a reservoir for human pandemics.

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.

Hepatitis C Virus Infection in Guinea-Bissau: A Sexually Transmitted Genotype 2 with Parenteral Amplification?

Background Sub-Saharan Africa is the continent with the highest prevalence of Hepatitis C virus (HCV) infection. Genotype 2 HCV is thought to have originated from West Africa several hundred years ago. Mechanisms of transmission remain poorly understood. Methodology/Principal Findings To delineate mechanisms for HCV transmission in West Africa, we conducted a cross-sectional survey of individuals aged ≥50 years in Bissau, Guinea-Bissau. Dried blood spots were obtained for HCV serology and PCR amplification. Prevalence of HCV was 4.4% (47/1066) among women and 5.0% (27/544) among men. In multivariate analysis, the independent risk factors for HCV infection were age (baseline: 50–59 y; 60–69 y, adjusted odds ratio [AOR]: 1.67, 95% CI: 0.91–3.06; ≥70 y, AOR: 3.47, 95% CI: 1.89–6.39), belonging to the Papel, Mancanha, Balanta or Mandjako ethnic groups (AOR: 2.45, 95% CI:1.32–4.53), originating from the Biombo, Cacheu or Oio regions north of Bissau (AOR: 4.16, 95% CI: 1.18–14.73) and having bought or sold sexual services (AOR: 3.60, 95% CI: 1.88–6.89). Of 57 isolates that could be genotyped, 56 were genotype 2. Conclusions Our results suggest that transmission of HCV genotype 2 in West Africa occurs through sexual intercourse. In specific locations and subpopulations, medical interventions may have amplified transmission parenterally.