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Development of microbicides for the prevention of HIV transmission in an in vivo system of debdritic cells and CD4+ T cells with emphasis on synergistic activity and avoidance of viral resistance
Maturation of a Trypanosoma brucei infection to the infectious metacyclic stage is enhanced in nutritionally stressed tsetse flies
We report on the effect of tsetse fly starvation on the maturation of an established Trypanosoma brucei brucei midgut infection, i.e., the development of procyclic infection into the infectious metacyclic parasites in the tsetse fly salivary glands. Glossina morsitans morsitans flies were nutritionally stressed 10 d after the uptake of a T. b. brucei-infected bloodmeal by depriving these flies from feeding for seven consecutive days, whereas the control fly group (nonstarved group) continued to be fed three times a week. After this period, both fly groups were again fed three times per week on uninfected rabbit. Thirty days after the infected bloodmeal, all surviving flies were dissected and examined for the presence of an immature midgut and a mature salivary gland trypanosome infections. Results showed a significantly increased proportion of flies with salivary gland infection in the nutritionally stressed fly group suggesting an enhanced maturation of the trypanosome infection. These data suggest that environmental factors that cause nutritional stress in a tsetse population do not only make tsetse flies significantly more susceptible to establish a midgut infection as was shown previously but also boost the maturation of these midgut infections
Nutritional stress affects the tsetse fly's immune gene expression
Tsetse-transmitted trypanosomiasis poses a serious threat to human and animal health in sub-Saharan Africa. The majority of tsetse flies (Glossina spp.) in a natural population will not develop a mature infection of either Trypanosoma congolense or Trypanosoma brucei sp. because of refractoriness, a phenomenon that is affected by different factors, including the tsetse fly's immune defence. Starvation of tsetse flies significantly increases their susceptibility to the establishment of a trypanosome infection. This paper reports the effects of nutritional stress (starvation) on (a) uninduced baseline levels of gene expression of the antimicrobial peptides attacin, defensin and cecropin in the tsetse fly, and (b) levels of expression induced in response to bacterial (Escherichia coli) or trypanosomal challenge. In newly emerged, unfed tsetse flies, starvation significantly lowers baseline levels of antimicrobial peptide gene expression, especially for attacin and cecropin. In response to trypanosome challenge, only non-starved older flies showed a significant increase in antimicrobial peptide gene expression within 5 days of ingestion of a trypanosome-containing bloodmeal, especially with T. brucei bloodstream forms. These data suggest that a decreased expression of immune genes in newly hatched flies or a lack of immune responsiveness to trypanosomes in older flies, both occurring as a result of fly starvation, may be among the factors contributing to the increased susceptibility of nutritionally stressed tsetse flies to trypanosome infection
Drug prescribing practices for tuberculosis in Uzbekistan
SETTING: Uzbekistan has had 100% DOTS coverage since 2005; however, the treatment success rate has remained at around 80% for the last 4 years. Surveys from the capital city of Tashkent and from western Uzbekistan have shown high levels of primary multidrug resistance. OBJECTIVE: To assess treatment regimens prescribed for new cases of tuberculosis (TB), including the prescription of additional non-TB drugs, and the cost implications for the patient. DESIGN: We randomly sampled 30 clusters of seven new TB patients. Enrolled patients were interviewed and their medical records were reviewed. RESULTS: In general, the treatment regimens prescribed were correct; doses were high rather than low. Second-line anti-tuberculosis drugs were rarely prescribed. In addition to anti-tuberculosis drugs, patients were prescribed on average seven to eight non-TB drugs. The rationale for prescribing the non-TB drugs was, however, questionable. Patients incurred substantial costs for these drugs, some of which were not without risk. CONCLUSION: Prescriptions of anti-tuberculosis drugs for new TB patients are adequate; however, the practice of prescribing additional non-TB drugs needs to be reconsidered
Early neurologic abnormalities associated with human T-cell lymphotropic virus type 1 infection in a cohort of Peruvian children
OBJECTIVE: Because human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may occur in some children infected with HTLV-1, we sought to determine the prevalence of neurologic abnormalities and any associations of neurologic abnormalities with infective dermatitis in these children. STUDY DESIGN: We enrolled 58 children infected with HTLV-1 and 42 uninfected children (ages 3 to 17) of mothers infected with HTLV-1 in a family study in Lima, Peru. We obtained medical and developmental histories, surveyed current neurologic symptoms, and conducted a standardized neurologic examination without prior knowledge of HTLV-1 status. RESULTS: HTLV-1 infection was associated with reported symptoms of lower extremity weakness/fatigue (odds ratio [OR], 6.1; confidence interval [CI], 0.7 to 281), lumbar pain (OR, 1.7; 95% CI, 0.4 to 8), and paresthesia/dysesthesia (OR, 2.6; CI, 0.6 to 15.8). HTLV-1 infection was associated with lower-extremity hyperreflexia (OR, 3.1; CI, 0.8 to 14.2), ankle clonus (OR, 5.0; CI, 1.0 to 48.3), and extensor plantar reflex (OR undefined; P = .2). Among children infected with HTLV-1, a history of infective dermatitis was associated with weakness (OR, 2.7; CI, 0.3 to 33), lumbar pain (OR, 1.3; CI, 0.2 to 8), paresthesia/dysesthesia (OR, 2.9; CI, 0.5 to 20), and urinary disturbances (OR, 5.7; CI, 0.5 to 290). CONCLUSIONS: Abnormal neurologic findings were common in Peruvian children infected with HTLV-1, and several findings were co-prevalent with infective dermatitis. Pediatricians should monitor children infected with HTLV-1 for neurologic abnormalities