Implementation of multidrug-resistant tuberculosis (MDR-TB) treatment in Gabon: lessons learnt from the field.

PURPOSE: Since May 2016, WHO recommended a 9-12 month short-treatment regimen for multidrug-resistant tuberculosis (MDR-TB) treatment known as the 'Bangladesh Regimen'. However, limited data exist on the appropriateness thereof, and its implementation in low- and middle-income countries (LMIC). We report here on the pilot phase of the evaluation of the Bangladesh regimen in Gabon, prior to its endorsement by the WHO. METHODS: This ongoing observational study started in September 2015. Intensive training of hospital health workers as well as community information and education were conducted. GeneXpert-confirmed MDR-TB patients received the second-line anti-tuberculosis drugs (4KmMfxPtoHCfzEZ/5MfxCfzEZ). Sputum smears and cultures were done monthly. Adverse events were monitored daily. RESULTS: Eleven patients have been treated for MDR-TB piloting the short regimen. All were HIV-negative and presented in poor health with extensive pulmonary lesions. The overall sputum culture conversion rate was 64% after 4 months of treatment. Three patients developed marked hearing loss; one a transient cutaneous rash. Of 11 patients in our continuous care, 7 (63.6%) significantly improved clinically and bacteriologically. One (9.1%) patient experienced a treatment failure, two (18.2%) died, and one (9.1%) was lost to follow up. CONCLUSIONS: Our pioneering data on systematic MDR-TB treatment in Gabon, with currently almost total absence of resistance against the second-line drugs, demonstrate that a 9-month regimen has the capacity to facilitate early culture negativity and sustained clinical improvement. Close adverse events monitoring and continuous care are vital to success.

Low incidence of the immune reconstitution inflammatory syndrome among HIV-infected patients starting antiretroviral therapy in Gabon: a prospective cohort study.

There is a paucity of data on the immune reconstitution inflammatory syndrome (IRIS) in the Central African region. We followed ART-naive HIV-infected patients initiating antiretroviral therapy in an HIV clinic in Gabon, for 6 months. Among 101 patients, IRIS was diagnosed in five. All IRIS cases were mucocutaneous manifestations. There were no cases of tuberculosis (TB) IRIS, but active TB (n = 20) was associated with developing other forms of IRIS (p = 0.02). Six patients died. The incidence of IRIS is low in Gabon, with mild, mucocutaneous manifestations.

Tuberculin skin test conversion among HIV patients on antiretroviral therapy in Uganda.

SETTING: A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence. OBJECTIVE: To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART). DESIGN: Prospective cohort study of TST-negative, ART-naïve HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed. RESULTS: Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings. CONCLUSIONS: A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART.

Low prevalence of vitamin D deficiency in Ugandan HIV-infected patients with and without tuberculosis.

OBJECTIVE: To examine whether hypovitaminosis D is a risk factor for the development of tuberculosis (TB) associated immune reconstitution inflammatory syndrome (IRIS). METHODS: We measured serum 25-hydroxyvitamin D (25D) concentrations in four groups of patients at Mulago Hospital, Kampala, Uganda: 1) patients co-infected with TB and the human immunodeficiency virus (HIV) receiving anti-tuberculosis treatment (HIV+TB+; n = 92) who did and did not develop TB-IRIS after starting antiretroviral treatment (ART), 2) HIV-infected patients without TB (HIV+TB-; n = 20) starting ART, 3) non-HIV-infected individuals with TB (HIV-TB+; n = 27), and 4) those without TB (HIV-TB-; n = 23). RESULTS: The prevalence of optimal 25D levels (>75 nmol/l) was as follows: 59% in HIV+TB+, 65% in HIV+TB-, 63% in HIV-TB+ and 35% in HIV-TB- patients. 25D concentrations decreased during the first 3 months of ART in HIV+TB+ individuals who developed IRIS (P = 0.005) and those who did not (P = 0.002), and in HIV+TB- individuals (P = 0.015); however, 25D concentration in patients who did or did not develop TB-IRIS did not differ. CONCLUSION: The prevalence of optimal vitamin D status was relatively high in HIV-infected patients with and without TB living near the equator. No difference in 25D concentrations was observed between TB-IRIS and non-IRIS. However, 25D concentrations decreased during ART.

Differences in immunoregulatory cytokine expression patterns in the systemic and genital tract compartments of HIV-1-infected commercial sex workers in Benin.

Initial exposure to human immunodeficiency virus type 1 (HIV-1) during heterosexual transmission occurs in the genital tract. Although much of the literature on the immune response to HIV-1 infection is based on studies performed at the systemic level, our understanding of tissue-specific immunity is lacking. Levels of both genital mucosal and blood interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma production were compared between 57 HIV-1-uninfected and 52 HIV-1-infected female commercial sex workers (CSWs) as well as 73 HIV-1-uninfected non-CSW control women at low risk for exposure. HIV-1-infected CSWs had significantly higher genital mucosal levels of TNF-alpha and IFN-gamma compared with those in both the HIV-uninfected CSW and non-CSW groups. In contrast, the serum levels of all the cytokines tested were lower in HIV-1-infected CSWs compared with those in the other groups. The increased production of genital mucosal pro-inflammatory cytokines in HIV-1-infected CSWs possibly reflects susceptibility to HIV-1 infection and disease progression/perpetuation at the initial site of exposure.

Persistent polyclonal B-cell lymphocytosis: further evidence for a genetic disorder associated with B-cell abnormalities.

Persistent polyclonal B-cell lymphocytosis (PPBL) is an intriguing disorder diagnosed predominantly in women, usually cigarette smokers, characterized by an increase in the number of polyclonal B lymphocytes. Abnormality of the B-cell population is also evidenced by the presence of multiple bcl-2/Ig gene rearrangements and the finding of an additional long arm chromosome 3q+ (i3)(q10) within a significant proportion of B cells. The physiopathology of PPBL is unknown but its association with the HLA DR7 phenotype suggests a possible genetic disorder. To further determine whether PPBL has a genetic predisposition, we have undertaken an extensive study in a large family of a patient diagnosed with PPBL. Three individuals among the first-degree relatives presented all the criteria for a diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was shown in two additional siblings. Multiple bcl-2/Ig gene rearrangements, a typical feature of PPBL, were identified in 8/10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and of a paternal HLA haplotype. We conclude that PPBL has a familial occurrence suggesting an underlying genetic defect. The development of the complete syndrome probably relies on unidentified additional co-factors.