Impact of genotypic drug resistance mutations on clinical and immunological outcomes in HIV-infected adults on HAART in West Africa

OBJECTIVES: To analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART has so far never been reported. METHODS: In 2004 in Abidjan, C?te d'Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/microl). RESULTS: At study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/microl; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/microl in patients with undetectable viral loads, +51 cells/microl in those with detectable viral loads with no mutations and +3 cells/microl in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19). CONCLUSION: In this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.     

Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome

RATIONALE: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax. OBJECTIVES: We evaluated 198 patients from 89 families with BHDS to characterize the risk factors for pneumothorax and genotype-pulmonary associations. METHODS: Helical computed tomography scans of the chest were used to screen for pulmonary abnormalities. BHD mutation data were used for genotype-pulmonary associations. We examined the relationship of pneumothorax with categorical parameters (sex, smoking history, and lung cysts) and continuous parameters (number of cysts, lung cyst volume, and largest cyst diameter and volume). Logistic regression analyses were used to identify the risk factors associated with pneumothorax. MEASUREMENTS AND MAIN RESULTS: Twenty-four percent (48/198) of patients with BHDS had a history of pneumothorax. The presence of lung cysts was significantly associated with pneumothorax (p = 0.006). Total lung cyst volume, largest cyst diameter and volume, and every parameter related to the number of lung cysts were significantly associated (p < 0.0001) with pneumothorax. A logistic regression analysis showed that only the total number of cysts in the right parenchymal lower lobe and the total number of cysts located on the pleural surface in the right middle lobe were needed to classify a patient as to whether or not he or she was likely to have a pneumothorax. Exon location of the BHD mutation was associated with the numbers of cysts (p = 0.0002). CONCLUSIONS: This study indicates that patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.     

The management of cerebrovascular events in Senegal

OBJECTIVES: Because of its acuteness and rapid progress to irreversible injury, stroke is a dramatically high priority medical emergency. The purpose of this prospective study was to ascertain the average time limit for primary management of stroke victims referred to the Senegalese national medical center considered as the final link within the country's healthcare organisation. PATIENTS AND METHODS: We reviewed the files of 170 patients aged 25-90 (average 61+/-13 years). The sex ratio was 0.68. Seventy percent of the patients resided in the nation's capital, Dakar. RESULTS: Most of the patients were referred to a medical center late. Admission was before the 6th hour for only one patient and none of the patients were admitted before the 3rd hour. Late treatment was related to the remoteness of medical centers. Among patients residing in Dakar, the first visit occurred between 6 and 24 hours for 30p.cent versus 7.8 p.cent for patients residing in rural areas of the country. Educational level and socio-economic status had no effect on late treatment. None of the patients were given prehospital care. Treatment was essentially symptomatic in patients with hemorrhagic stroke. Anticoagulants or anti-platelet agents were prescribed for patients with ischemic stroke. Only 29.4 p.cent of patients were given rehabilitation care. Mortality was 50.6 p.cent and the rate of dependency 41.7 p.cent. CONCLUSION: In Senegal, stroke victims receive care too late. This situation arises because of insufficiency of human and material resources and inaccessibility to care centers.     

Alloreactivity and association of human natural killer cells with the major histocompatibility complex

All NK cells potentially lytic for autologous cells but not expressing self-major histocompatibility complex (MHC)-reactive receptors could be eliminated by a negative selection mechanism during ontogeny. This idea is based on the existence of a NK cell subset expressing a specific inhibitory receptor for allogeneic MHC alleles. As ancestral haplotypes of the MHC appear to define identical MHC haplotypes in unrelated individuals, unrelated individuals having the same ancestral haplotype should also have the same NK-defined allospecificities that have been shown to map to the human MHC. To test this prediction, multiple cell lines from unrelated individuals having the same ancestral haplotypes were tested for the NK-defined allospecificities. It was found that cells having the same ancestral haplotypes do have the same NK-defined specificities. Furthermore, the NK-defined phenotype of cells that possess two different ancestral haplotypes can be predicted from the NK-defined phenotypes of unrelated cells that are homozygous for the ancestral haplotypes concerned. Although the group 1 and 2 NK-defined allospecificities can be explained to some extent by HLA-C alleles, evidence is presented that additional genes may modify the phenotype conferred by HLA-C.     

Clinical impact and cost-effectiveness of co-trimoxazole prophylaxis in patients with HIV/AIDS in Côte d'Ivoire: a trial-based analysis

BACKGROUND: In 2000, WHO/UNAIDS recommended co-trimoxazole prophylaxis for persons at early stages of HIV infection (WHO stage > or = 2) in sub-Saharan Africa. OBJECTIVE: To assess the cost-effectiveness of alternative strategies for initiation of co-trimoxazole in C?te d'Ivoire. DESIGN: Cost-effectiveness analysis with an HIV simulation model using clinical and cost data from a randomized trial of co-trimoxazole in HIV-infected adults. METHODS: The study included HIV-infected patients in C?te d'Ivoire, with median age 33 years. Thirty-four percent were classified as WHO stage 2, 59% as stage 3, and 7% as stage 4. The mean CD4 cell count was 331 x 10(6) cells/l. The interventions were no prophylaxis, clinical criteria-based co-trimoxazole initiation (early: WHO stage > or = 2; late: WHO stage > or = 3), CD4-based co-trimoxazole initiation (< 500, < 200, < 50 x 10(6) CD4 cells/l). The outcome measures were life expectancy, lifetime costs, and incremental cost-effectiveness. RESULTS: The most effective strategy, initiation of co-trimoxazole prophylaxis at WHO stage > or = 2, increased undiscounted life expectancy by 5.2 months, discounted life expectancy by 4.4 months, and lifetime costs by US dollars 60, compared with no prophylaxis. Delaying prophylaxis initiation until WHO stage >or = 3 was less costly and less effective. All CD4-based strategies were dominated. The incremental cost-effectiveness of early versus late co-trimoxazole prophylaxis initiation was US dollars 200/year of life gained. Results were stable despite wide variations in plausible assumptions about bacterial resistance and the prophylaxis efficacy on co-trimoxazole-resistant strains. CONCLUSIONS: For HIV-infected adults in C?te d'Ivoire, co-trimoxazole prophylaxis is reasonably cost-effective and most effective if initiated when WHO stage > or = 2. Early co-trimoxazole prophylaxis will prevent complications prior to antiretroviral therapy initiation and should be considered an essential component of care for early HIV in sub-Saharan Africa.     

Tumoral mycetoma of the buttock

BACKGROUND: Mycetomas are actinomycosic or fungal infections where the infectious agent produces grains. We report an atypical case of fungal mycetoma presenting as a tumoral formation on the buttock. CASE REPORT: A 56-year-old unemployed man from the Diourbel region of central Senegal consulted in February 1997 for a fistulalized tumor of the right buttock which had developed spontaneously and progressed for 5 years. The patient's general health remained satisfactory. Physical examination showed a voluminous 25 cm tumefaction extending from the right buttock to the perineum. The tumor showed a few areas of fistualization which discharged black grains under pressure. There was a 1.5 cm right inguinal node which did not appear to be inflammatory. The remainder of the physical examination was normal. Pathology reported inflammatory connective tissue surrounding a brownish polycyclic grain composed of spores and mycele filaments. The diagnosis of fungal mycetoma was retained and surgical excision under general anesthesia was performed. DISCUSSION: This is an atypical case of fungal mycetoma because of its tumoral form and gluteal localization. The differential diagnosis was cutaneous neurofibroma, myoma, or Darier-Ferrand dermatofibrosarcoma. The frequency of extrapodal red grain mycetomas has been pointed out by several authors from Senegal, but extrapodal black grain forms as seen in our case are more exceptional.     

Respiratory manifestations in HIV-infected children pre- and post-HAART in Abidjan, the Ivory Coast

Among children infected with human immunodeficiency virus (HIV), respiratory diseases are a frequent cause of morbidity and mortality. This review describes respiratory manifestations of paediatric HIV infection before and after the beginning of HAART in Abidjan, Ivory Coast. In an observational cohort, HIV infected children had quarterly clinical visits and a day-clinic available all week for ill children. CD4 and viral load were measured at baseline and every 6 months thereafter. All children with a CD4 percentage below 25% were prescribed daily cotrimoxazole prophylaxis. Ninety-eight children (of a total of 282) were recruited before HAART and treated during the follow-up, there were 56 boys and 42 girls, with a mean age of 6.2 years at inclusion. The mean percentage of CD4 before HAART was 8.7%. Twelve children had a history of pulmonary tuberculosis and five were on antituberculosis treatment at inclusion. Fifty-one per cent presented with abnormalities on chest X-ray at inclusion. Before initiation of HAART, respiratory manifestations represented 32.4% of morbidity events and the incidence for 100 child/months was 9.29 for URTI, 15.2 for bronchitis, 6.07 for LRTI, 0.71 for tuberculosis and 0.36 for Pneumocystis carinii. After the initiation of HAART, respiratory manifestations represented 40.9% of all morbidity events and the incidence for 100 child/months was 5.35 for URTI, 9.48 for bronchitis, 2.17 for LRTI and 0.16 for tuberculosis. During HAART treatment, the incidence of respiratory infections decreased dramatically compared to before the antiretroviral treatment. However, respiratory events still represented 40% of all events occurring following the start of HAART therapy.     

Pattern of type A hemophilia in Senegal: prospective study in 54 patients]

Little is known about hemophilia in the developing countries because of the difficulties in the diagnosis and the therapeutical management of this disease. Here we present the results of the follow-up of 54 patients in Senegal. Diagnosis was always confirmed by measuring the biological activity of factors VIII and IX. Patients were treated at home or in the hematology service according to the gravity of hemorrhage events. The severe form represented 29.6%, moderate form was 55.6% and minor form 14.8%. Total number of hemorrhage events was 1078 per year: 449 hemarthrosis (41.7%), 373 exteriorized hemorrhage (34.7%) and 256 hematomas (23.7%). Mean frequency of hemarthrosis per patient per year was 12 in severe form, 8 in moderate form and 3 in minor form. Mean frequency of hematomas per patient per year was 5.2 in severe, 4.9 in moderate and 4.2 in minor form. For exteriorized hemorrhage, the mean frequency was 7.06 in severe, 7.4 in moderate and 6.5 in minor form. The severity of hemophilia significantly influenced the frequency of hemarthrosis (P = 0.02) but not the frequency of hematoma (P = 0.6) and exteriorized hemorrhage (P = 0.6). Treatment of these accidents was performed at home (88.5%), in day hospital (9.5%) or needed hospitalization (1.8%). Three patients have died during this three-year survey, one because of HIV infection and the two others from digestive hemorrhage. In conclusion, lesser morbidity and mortality were observed when compared with previously. The importance of a regular follow up and education of patients must be emphasized especially if factor concentrates are not available.