HIV epidemic in Central African Republic: high prevalence rates in both rural and urban areas

A sentinel serosurveillance study was conducted in Central African Republic to estimate the prevalence of HIV seropositivity in the general adult population in each province so that the public health authorities can target HIV prevention programmes to the priority areas. Blood samples were collected from women attending 48 antenatal clinics in urban and rural areas of the Central African Republic. These samples were tested for HIV antibodies in an anonymous and unlinked manner using strategy II recommended by WHO. The data were extrapolated to all women of reproductive age in Central African Republic by use of a parity-based adjustment involving the application of correction factors to the observed prevalence rates. A total of 9,305 pregnant women were recruited from November 2001 to October 2002. HIV seroprevalence was high in all age groups (12% in the less than 20 year age group to 17% in the 25-29 year age group). The median prevalence of HIV in antenatal clinics was similar for rural areas, for Bangui and for other urban areas (16.5, 15.0, and 12.5% respectively). Adjustment for parity and fertility pattern increased the prevalence of HIV in all antenatal clinics except in Bangui. This first national study of HIV prevalence in Central African Republic revealed that the HIV epidemic is continuing to spread in both urban and rural areas. Thus, efforts to reduce transmission should be made in every part of the country.     

Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression

Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4⁺ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4⁺ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.     

Combination of WAGR and Potocki-Shaffer contiguous deletion syndromes in a patient with an 11p11.2-p14 deletion

Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome. The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated. We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity. She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6. This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested. Molecular and follow-up data on the original WAGRO case are briefly presented.     

Epidemiology and genetic characterization of HIV-1 isolates in the general population of Djibouti (Horn of Africa)

During a national survey in 2002 in Djibouti, serum samples were collected using a valid sampling scheme from 2423 Djiboutians representing the general population of urban and rural districts. The HIV-1 seroprevalence was 2%. The HIV-1 polymerase gene from 53 untreated patients was amplified. Phylogenetic analysis of 34 isolates revealed a majority of subtype C (73%) as well as other subtypes, including CRF02_AG recombinants (18%), subtype D (6%), and subtype A (3%).     

X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

We describe a family with an X-linked dominant chondrodysplasia. Four males and six females were affected through four generations. Identification of skeletal abnormalities and hydrocephaly during the pregnancy of three male fetuses led to termination of the pregnancies. A fourth affected male died at 6 days of life. The four patients had chondrodysplasia, hydrocephaly, and facial features with microphthalmia. Radiographs showed severe platyspondyly and various bone abnormalities including a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. The affected females were less affected and showed small stature, sometimes associated with body asymmetry and mild mental retardation. This condition appears to be a previously unrecognized X-linked dominant chondrodysplasia.     

Kinetics of Antibody Responses in Rickettsia africae and Rickettsia conorii Infections

African tick-bite fever, caused by Rickettsia africae, is the most common tick-borne rickettsiosis in sub-Saharan Africa. Mediterranean spotted fever due to Rickettsia conorii also occurs in the region but is more prevalent in Mediterranean countries. Using microimmunofluorescence, we compared the development of immunoglobulin G (IgG) and IgM titers in 48 patients with African tick-bite fever and 48 patients with Mediterranean spotted fever. Doxycycline treatment within 7 days from the onset of disease significantly prevented the development of antibodies to R. africae. In patients with African tick-bite fever, the median times to seroconversion with IgG and IgM were 28 and 25 days, respectively, after the onset of symptoms. These were significantly longer by a median of 6 days for IgG and 9 days for IgM than the times for seroconversion in patients with Mediterranean spotted fever (P < 10⁻²). We recommend that sera collected 4 weeks after the onset of signs of patients with suspected African tick-bite fever should be used for the definitive serological diagnosis of R. africae infections.     

Pathology of inverted Takotsubo cardiomyopathy

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. The inverted Takotsubo pattern has been recently recognized as a novel heart neurologic stress-related syndrome. We report on the case of a 40-year-old woman presenting with massive subarachnoid hemorrhage and brain death. Echocardiography revealed an extensive left ventricular circumferential akinesis except at the apex. Histologic analysis of the heart confirmed the absence of myocardial infarction and revealed only sparse foci of myocyte necrosis with contraction bands in the akinetic areas.     

Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients

BACKGROUND: Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations. OBJECTIVE: To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy. STUDY DESIGN: Thirteen patients received foscarnet at a fixed dose of 80mg/kg twice daily for 14 days, in combination with zidovudine or stavudine. RESULTS: The baseline median HIV viral load and CD4 cell count were 5.10log(10)copies/ml and 23cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs. CONCLUSIONS: These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.     

Use of an automated multiple-locus, variable-number tandem repeat-based method for rapid and high-throughput genotyping of Staphylococcus aureus isolates

Fast and reliable genotyping methods that allow real-time epidemiological surveillance would be instrumental to monitoring of the spread of methicillin-resistant Staphylococcus aureus. We describe an automated variable-number tandem repeat-based method for the rapid genotyping of Staphylococcus aureus. Multiplex PCR amplifications with eight primer pairs that target gene regions with variable numbers of tandem repeats were resolved by microcapillary electrophoresis and automatically assessed by cluster analysis. This genotyping technique was evaluated for its discriminatory power and reproducibility with clinical isolates of various origins, including a panel of control strains previously characterized by several typing methods and collections from either long-term carriers or defined nosocomial outbreaks. All steps of this new procedure were developed to ensure a rapid turnaround time and moderate cost. The results obtained suggest that this rapid approach is a valuable tool for the genotyping of S. aureus isolates in real time.     

Coxiella burnetii Induces Reorganization of the Actin Cytoskeleton in Human Monocytes

Coxiella burnetii, an obligate intracellular bacterium which survives in myeloid cells, causes Q fever in humans. We previously demonstrated that virulent C. burnetii organisms are poorly internalized by monocytes compared to avirulent variants. We hypothesized that a differential mobilization of the actin cytoskeleton may account for this distinct phagocytic behavior. Scanning electron microscopy demonstrated that virulent C. burnetii stimulated profound and polymorphic changes in the morphology of THP-1 monocytes, consisting of membrane protrusions and polarized projections. These changes were transient, requiring 5 min to reach their maximum extent and vanishing after 60 min of incubation. In contrast, avirulent variants of C. burnetii did not induce any significant changes in cell morphology. The distribution of filamentous actin (F-actin) was then studied with a specific probe, bodipy phallacidin. Virulent C. burnetii induced a profound and transient reorganization of F-actin, accompanied by an increase in the F-actin content of THP-1 cells. F-actin was colocalized with myosin in cell protrusions, suggesting that actin polymerization and the tension of actin-myosin filaments play a role in C. burnetii-induced morphological changes. In addition, contact between the cell and the bacterium seems to be necessary to induce cytoskeleton reorganization. Bacterial supernatants did not stimulate actin remodeling, and virulent C. burnetii organisms were found in close apposition with F-actin protrusions. The manipulation of the actin cytoskeleton by C. burnetii may therefore play a critical role in the internalization strategy of this bacterium.