Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi's sarcoma and other diseases.

BACKGROUND: Infection with human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma (KS)-associated herpesvirus, is associated with all forms of KS, with primary effusion lymphoma (PEL), and with some forms of multicentric Castleman's disease (MCD), but the pathogenic role of HHV8 in these tumors and the clonal nature of KS are still unclear. The purpose of this study was to examine whether the number of terminal repeats (TRs) contained in the fused TR region of HHV8 could be used as a marker of clonality in HHV8-associated tumors. METHODS: Pulsed-field gel electrophoresis (PFGE) and multiple-probe Southern blot analysis of the HHV8 TR region were performed on high-molecular-weight DNA obtained from tumoral KS, PEL, and MCD lesions. RESULTS: These analysis showed that the fused TR region contains a large but variable number of TR units (ranging from 16 to 75) and that the viral genome is present as extrachromosomal circular DNA in these tumors in vivo, with occasional ladders of heterogeneous linear termini reflecting lytic replication. All PEL tumors and PEL-derived cell lines as well as some KS tumors contained monoclonal or oligoclonal fused TR fragments; however, the TR region appeared polyclonal in MCD tumors and in a few KS lesions. CONCLUSION: Several KS and PEL lesions are monoclonal expansions of a single infected cell, suggesting that HHV8 infection precedes tumor growth and thus supporting an etiologic role of latent HHV8 in these proliferations. Our finding that nodular KS lesions display all possible patterns of clonality supports the model according to which KS begins as a polyclonal disease with subsequent evolution to a monoclonal process.

[A case of tuberculous otitis media associated with meningoencephalitis in the Bangui paediatric institution (Central African Republic)]. / A propos d'un cas d'otite tuberculeuse primitive compliquée de méningoencéphalite au complexe pédiatrique de Bangui (République centrafricaine).

The authors report a case of fatal tuberculous meningoencephalitis following chronic bilateral otitis media in a child. Mycobacterium tuberculosis was identified in the CSF and in the otitis secretions. There were no pulmonary tuberculosis signs, thus the tuberculous otitis was considered as primary. In high tuberculosis endemic areas like Central African Republic it is important to consider tuberculosis, in chronic otitis media resistant to non specific therapy, and to reinforce the immunization programs for children.

[Tuberculosis and HIV co-infection among children hospitalized in Bangui (Central African Republic)]. / Co-infection tuberculose et virus de l'immunodéficience humaine chez les enfants hospitalisés à Bangui (République Centrafricaine).

INTRODUCTION: Tuberculosis associated with HIV-infection in children makes the diagnosis of tuberculosis more complicated since it is already difficult to establish because clinically based in low-income countries, and worsens its outcome under treatment. We report our experience from the paediatric clinics of Bangui, Central African Republic. PATIENTS AND METHODS: Our retrospective study analyzed 18-month -to 15-year-old children treated for tuberculosis from April 1998 to June 2000. Diagnosis and outcome data were abstracted from patient medical reports and we compared seropositive and seronegative patients. RESULTS: Globally, 284 cases have been analyzed. HIV-infection rate was 25.7% (95% CI: 20.7-31.2%). Pulmonary tuberculosis and mixed forms rates were 94.4% (N = 268). Extrapulmonary tuberculosis was essentially lymphadenopathies which have been restricted only to seronegative patients. Tuberculosis microbiological findings were significantly lower in seropositive patients compared with seronegative ones, for microscopy (8.2 vs 24.6%) and for culture (35.6 vs 58.5%) (P-value < 0.05). On 28 seropositive and 72 seronegative children for which outcomes were registered, mortality rate was higher in seropositive than in seronegative patients (57.1 vs 19.4% respectively, P-value < 0.05). CONCLUSION: The authors suggest that diagnosis of tuberculosis should be strengthened by blood or lymph node puncture culture particularly for HIV-infected children and that the treatment outcomes could be improved by diagnosis and treatment of other opportunistic infections.

Surveillance of drug-resistant childhood tuberculosis in Bangui, Central African Republic.

SETTING: Bangui, the capital of the Central African Republic, where overall drug resistance and multidrug resistance among adult new tuberculosis (TB) cases were respectively 16.4% and 1.1% in 1998. OBJECTIVE: To determine the prevalence of drug resistance among children with tuberculosis and to compare the epidemiological and clinical features of TB in children with drug-resistant and drug-susceptible TB. METHODS: All strains of Mycobacterium tuberculosis obtained from children aged 0-15 years at Bangui Paediatric Hospital were prospectively collected from April 1998 to June 2000, and susceptibility testing was performed for each specimen. The children's epidemiological and clinical data were recorded. RESULTS: Susceptibility results were available for 165/190 children with M. tuberculosis. Overall drug resistance and multidrug resistance were 15.2% and 0.6%, respectively. Isoniazid and streptomycin were the only drugs associated with TB monoresistance. No significant difference was found in the epidemiological or clinical data of children infected with a resistant strain and those infected with a susceptible strain. CONCLUSION: The prevalence of drug resistance in childhood is similar to that observed in adult new TB cases in the same period. Surveillance will continue to be performed in Bangui periodically to assess the trend of true drug resistance among new TB cases.

[Resurgence of yaws in Central African Republic. Role of the Pygmy population as a reservoir of the virus]. / Résurgence du pian en République centrafricaine. Rôle de la population pygmée comme réservoir de virus.

The authors present the results of a clinical (framboesia) and serological (TPHA and VDRL) investigation aimed at defining the reservoir of virus of yaws in the Lobaye area (southwest of CAR) out of which the disease spreads in spite of previous mass treatment campaigns. The Lobaye focus is still active because we found among the pediatric population under the age of 15 years, 5.6% contagious skin lesion and 19.6% VDRL+. In this area with contact between nomadic Pygmies and sedentary ethnic groups, the observed level of clinical and serological attacks suggested that the pygmie population, as previously described, makes up the principal focus of yaws. For every 1 case found through clinical examination, 3.5 cases VDRL+ and 4.8 cases TPHA+ are found through serological examination. This proportion indicates that clinical screening alone is not sufficient to evaluate the endemic yaws level in a population.

[First cases of imported cutaneous leishmaniasis in Bangui Central African Republic: efficacy of metronidazole]. / Premier cas de leishmaniose cutaneé d'importation à Bangui en République Centrafricaine: efficacité du métronidazole.

Cutaneous leishmaniasis is an uncommon disease in the Central African Republic (CAR). The purpose of this report is to present a case that was imported into Bangui, CAR from the neighboring Republic of Chad. The polymorphous aspects of lesions and the spectrum of laboratory findings associated with the disease in this patient are described. Oral treatment with metronidazole led to rapid resolution with minimal scarring.

[Tuberculosis and HIV in Bangui, Central African Republic: strong prevalence and management difficulties]. / Tuberculose et VIH à Bangui, République centrafricaine: forte prévalence et difficultés de prise en charge.

The increasing incidence of tuberculosis in relation with the HIV-AIDS epidemic poses a major public health problem in sub-Saharan Africa. The purpose of this retrospective study was to analyze the prevalence of HIV-1 infection, clinical presentation, and bacteriological findings in patients treated for tuberculosis in a hospital department in Bangui, Central African Republic between January 1996 and December 1998. Among the 1142 patients who benefited for HIV serology, HIV-1 prevalence of was 82% (IC95%: 79-85%). Most patients (92%), had not undergone HIV serology before hospitalization. Mean age was 34 years. Sex ratio F/M was 1.21. Diagnosis of tuberculosis was based mainly on clinical and radiological data. Positive sputum smears were available for only 52% of the patients. The most frequent site of tuberculosis was the lungs with no significant difference between the HIV-positive and HIV-negative groups (83% versus 79% respectively). Sputum-smear examination was positive in 42% of the patients with no significant difference between the HIV-positive and HIV-negative groups (43% versus 37%). Upon admission patients usually presented advanced disease, with 11% dying within a week after hospitalization. There was a steep increase in the prevalence of HIV in tuberculosis-infected patients in Banqui, from 32% in 1988 to 62% in 1994. In spite of the existence of a National Tuberculosis Control Program, diagnostic facilities remain limited and diagnosis of tuberculosis and HIV-infection is often delayed. Outpatient care must be improved.

Rapid identification of multidrug-resistant tuberculosis isolates in treatment failure or relapse patients in Bangui, Central African Republic.

Multidrug-resistant (MDR) strains were identified in 40% of 54 strains from patients presenting with tuberculosis (TB) treatment failure or relapse in Bangui, Central African Republic. Results obtained with the MTBDRplus line-probe assay or rpoB sequencing were 86% concordant with rifampicin (RMP) resistant phenotypes, while the amplification refractory mutation system test was 71% concordant. No mutation was found in RMP-susceptible strains. MTBDRplus and sequencing were concordant with the detection of the S315T mutation in katG in 95% of MDR strains. Sequencing of pncA suggested pyrazinamide resistance in 50% of MDR strains. Knowledge of these resistances should help to implement treatment in low-income countries.

High mortality rates among patients with tuberculosis in Bangui, Central African Republic.

PIP: Survival time until death was investigated in a prospective cohort of 224 tuberculosis patients from Bangui, Central African Republic, who were randomly selected from among 1492 such patients registered in 1993 and 1994. 6 patients (2.7%) presented with extrapulmonary tuberculosis, 186 (83%) were smear-positive, and 139 (62%) were infected with HIV-1. 23 (10.3%) had multidrug-resistant tuberculosis strains. The treatment regimen (isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and ethambutol for another 6 months) was successful in 46.4% of HIV-infected patients compared with 67.1% of HIV-negative patients. At the end of 8 months, 39.1% of HIV-infected patients but only 8.2% of HIV-negative patients had died. 24 months after the start of tuberculosis treatment, the cumulative death rate was 58% in HIV-seropositive patients compared with 20% in seronegative patients. Median life expectancy to death among HIV-infected tuberculosis patients was 15 months. Decreased survival was significantly associated with HIV-seropositivity, older age, failure to complete the full treatment regimen, and a low CD4 cell count. Multidrug-resistant tuberculosis was not linked to increased mortality.^ieng

Molecular epidemiology of human herpesvirus 8 in africa: both B and A5 K1 genotypes, as well as the M and P genotypes of K14.1/K15 loci, are frequent and widespread.

We have studied 52 new HHV8 strains by sequencing the complete hypervariable K1 gene and genotyping the K14.1/K15 loci located at both sides, respectively, of the viral genome. The samples originated from 49 patients with Kaposi's sarcoma (KS; 32 patients), multicentric Castleman's disease (MCD; 12 patients), or primary effusion lymphoma (PEL; 5 patients). Among these patients, 32 were of African origin (West and Central African countries and Creoles from French Guiana) and the 17 others were mostly French homosexuals. Comprehensive phylogenetic studies allowed the identification of distinct groups within the three already known main subtypes. Interestingly, two new sequences that did not cluster within a known subtype or group could be considered as prototypes of early/ancient variants of the C subtype and A/C set, respectively. Among the 32 African strains, the majority were either of the B subtype (13 cases) or of the A5 group (11 cases), indicating that this latter genotype is frequent and widespread in Africa. In contrast, a subtype C strain infected most of the 17 other patients. PCR-based genotyping of the K14.1/K15 loci revealed an overall predominance of P subtype, except in the A5 and B K1 groups, in which the P and M alleles were equally represented. The implications of these data on the evolution and spread of HHV8 among human African populations are discussed.