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Learning and doing: operational research and access to HIV treatment in Africa [editorial]
No full textMonitoring for treatment failure in patients on first-line antiretroviral treatment in resource-constrained settings
No full textPURPOSE OF REVIEW: The number of people living with HIV in low-income and middle-income countries (LMICs), who will fail first-line treatment and benefit from regimen switching, will steadily increase in the coming years. The diagnosis of treatment failure in many settings is challenging because of limited access to plasma HIV RNA testing. This article summarizes recent studies in LMICs, investigating the diagnosis of treatment failure. RECENT FINDINGS: WHO recommended clinico-immunological criteria to identify first-line treatment failure, which have a low sensitivity and positive predictive value. The addition of adherence criteria or alternative clinical and laboratory markers improves performance, but overall the results are suboptimal. This situation leads to both delayed and inappropriately premature switching to more expensive second-line agents. The cost-effectiveness of alternative monitoring strategies is debated, but there is increasing interest in the use of viral load testing to confirm virological failure before switching to second-line therapy. However, access to viral load testing in LMICs remains limited and a simple point-of-care assay is not yet available. SUMMARY: Monitoring the efficacy of antiretroviral therapy in LMICs remains a critical challenge. Current research priorities include the development of simpler, cheaper assays and optimizing monitoring strategies based on currently available technologies
Breteau Index threshold levels indicating risk for dengue transmission in areas with low Aedes infestation
No full textWe used Breteau Indices to – retrospectively – predict dengue transmission. The presence of one house
block (on average about 50 houses) with a Breteau Index ‡4 in a neighbourhood (a block plus the surrounding blocks in a radius of 100 m) predicted transmission at the latter level with 81.8% sensitivity and 73.3% specificity during the first month of the Havana 2001 dengue outbreak. This result
corroborates the external validity of this threshold, at least in situations with low infestations levels
In vivo parasitological measures of artemisinin susceptibility
No full textParasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24
Low-level CD4+ T cell activation in HIV-exposed seronegative subjects: influence of gender and condom use
No full textImmune activation has been suggested to increase susceptibility to human immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it could be deemed essential for mounting an effective antiviral immune response. In this study, we compared levels of T cell activation between exposed seronegative (ESN) partners in HIV-1 discordant couples and HIV-unexposed control subjects in Dakar, Senegal. ESN subjects showed lower levels of CD38 expression on CD4(+) T cells than did control subjects. However, this was found to be associated with concurrent differences in the use of condoms: ESN subjects reported a higher degree of condom use than did control subjects, which correlated inversely with CD38 expression. In addition, we observed markedly higher levels of T cell activation in women compared with men, irrespective of sexual behavior. These findings question the relevance of low-level CD4(+) T cell activation in resistance to HIV-1 infection and underscore the need to take gender and sexual behavior characteristics of high-risk populations into account when analyzing correlates of protective immunity
Dinocampus coccinellae as a parasitoid of the invasive ladybird Harmonia axyridis in Europe
No full textThe enemy release hypothesis states that the absence of effective natural enemies can be a fundamental aspect leading to the successful establishment of an invasive species. This study investigates the impact of the native braconid parasitoid Dinocampus coccinellae on European populations of the invasive ladybird Harmonia axyridis. The parasitoid attacked adults and fourth instars of the ladybird more frequently than pupae and third instars. When given a choice, D. coccinellae attacked non-melanic adults and adults of a long term laboratory population of H. axyridis more often than melanic adults and adults of a field population, respectively. However, in no choice tests the parasitoid attacked individuals of either morph type and of the field and laboratory populations with the same frequency. Immature development of D. coccinellae took longer at lower temperatures and when less advanced developmental host stages (larvae and pupae) were successfully parasitized. The parasitoid emergence rates ranged from 0% to 14.7% on field populations of H. axyridis depending on life stage of the host attacked and up to 16.9% when adults of a long term laboratory population were attacked. Successfully parasitized ladybirds showed reduced reproductive capacities (6–12% of unparasitized individuals) and aphid consumption rates (85% of unparasitized individuals), but these effects together with the low emergence rates of the parasitoid suggest that D. coccinellae may only have a marginal impact on the population growth of H. axyridis in Europe
Plasmodium knowlesi malaria in Vietnam: some clarifications
No full textA recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed
The central role of macrophages in trypanosomiasis-associated anemia: rationale for therapeutical approaches
No full textBovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.e. trypanosusceptibility versus trypanotolerance) will be discussed. In essence, while persistence of classically activated macrophages (M1) contributes to anemia development, switching towards alternatively activated macrophages (M2) alleviates pathology including anemia. Secondly, while parasite-derived glycolipids such as the glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1-mediated inflammation, promotes M2 development and prevents anemia development. In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI-based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing regulatory T cells will be discussed. Finally, the crucial role of iron-homeostasis in trypanosomiasis-associated anemia development will be documented to stress the analogy with anemia of chronic disease (ACD), hereby providing new insight that might contribute to the treatment of ACD