A randomized open study to assess the efficacy and tolerability of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Cambodia.

OBJECTIVES: To compare the efficacy and tolerability of dihydroartemisinin-piperaquine (DHA-PQP) with that of a 3-day regimen of mefloquine and artesunate (MAS3) for the treatment of uncomplicated falciparum malaria in Cambodia. METHOD: Randomized open-label non-inferiority study over 64 days. RESULTS: Four hundred and sixty-four patients were included in the study. The polymerase chain reaction genotyping-adjusted cure rates on day 63 were 97.5% (95% confidence interval, CI, 93.8-99.3) for DHA-PQP and 97.5% (95% CI, 93.8-99.3) for MAS3, P = 1. There were no serious adverse events, but significantly more episodes of vomiting (P = 0.03), dizziness (P = 0.002), palpitations (P = 0.04), and sleep disorders (P = 0.03) reported in the MAS3 treatment group, consistent with the side-effect profile of mefloquine. CONCLUSIONS: DHA-PQP was as efficacious as MAS3, but much better tolerated, making it more appropriate for use in a routine programme setting. This highly efficacious, safe and more affordable fixed-dose combination could become the treatment of choice for Plasmodium falciparum malaria in Cambodia

Does One Size Fit All? Drug Resistance and Standard Treatments: Results of Six Tuberculosis Programmes in Former Soviet Countries.

SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary

Providing universal access to antiretroviral therapy in Thyolo, Malawi through task shifting and decentralization of HIV/AIDS care.

Objective  To describe how district-wide access to HIV/AIDS care was achieved and maintained in Thyolo District, Malawi. Method  In mid-2003, the Ministry of Health and Médecins Sans Frontières developed a model of care for Thyolo district (population 587 455) based on decentralization of care to health centres and community sites and task shifting. Results  After delegating HIV testing and counseling to lay counsellors, uptake of testing increased from 1300 tests per month in 2003 to 6500 in 2009. Shifting responsibility for antiretroviral therapy (ART) initiations to non-physician clinicians almost doubled ART enrolment, with a majority of initiations performed in peripheral health centres. By the end 2009, 23 261 people had initiated ART of whom 11 042 received ART care at health-centre level. By the end of 2007, the universal access targets were achieved, with nearly 9000 patients alive and on ART. The average annual cost for achieving these targets was €2.6 per inhabitant/year. Conclusion  The Thyolo programme has demonstrated the feasibility of district-wide access to ART in a setting with limited resources for health. Expansion and decentralization of HIV/AIDS service-capacity to the primary care level, combined with task shifting, resulted in increased access to HIV services with good programme outcomes despite staff shortages

Combining causal model and focus group discussions experiences learned from a socio-anthropological research on the differing perceptions of caretakers and health professionals on children's health (Bolivia/Peru)

The paper discusses the utility of constructing causal models in focus groups. This was experienced as a complement to an in-depth ethnographic research on the differing perceptions of caretakers and health professionals on child's growth and development in Peru and Bolivia. The rational, advantages, difficulties and necessary adaptations of combining the two techniques are discussed on the basis of concrete examples. Authors conclude that the building of a causal model in a focus group session can be useful in comparing lay etiologies of diseases as perceived by different categories of caretakers and health professionals and in identifying specific health risks faced by children. Causal model building in a focus group can help renew discussions and participants'interest but its use is only justified when the study concerns the perception of the causality of a given phenomenon

Human African trypanosomiasis amongst urban residents in Kinshasa: a case-control study.

BACKGROUND: Increasing numbers of human African trypanosomiasis (HAT) cases have been reported in urban residents of Kinshasa, Democratic Republic Congo since 1996. We set up a case-control study to identify risk factors for the disease. METHODS: All residents of the urban part of Kinshasa with parasitologically confirmed HAT and presenting for treatment to the city's specialized HAT clinics between 1 August, 2002 and 28 February, 2003 were included as cases. We defined the urban part as the area with contiguous habitation and a population density >5000 inhabitants per square kilometre. A digital map of the area was drawn based on a satellite image. For each case, two serologically negative controls were selected, matched on age, sex and neighbourhood. Logistic regression models were fitted to control for confounding. RESULTS: The following risk factors were independently associated with HAT: travel, commerce and cultivating fields in Bandundu, and commerce and cultivating fields in the rural part of Kinshasa. No association with activities in the city itself was found. DISCUSSION: In 2002, the emergence of HAT in urban residents of Kinshasa appears mainly linked to disease transmission in Bandundu and rural Kinshasa. We recommend to intensify control of these foci, to target HAT screening in urban residents to people with contact with these foci, to increase awareness of HAT amongst health workers in the urban health structures and to strengthen disease surveillance

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

The epidemiology of Leishmania donovani infection in high transmission foci in India.

OBJECTIVE: Visceral Leishmaniasis (VL) is highly prevalent in Bihar, India. India and its neighbours aim at eliminating VL, but several knowledge gaps in the epidemiology of VL may hamper that effort. The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar. METHODS: Demographic and immunological surveys were carried out in July and November 2006, respectively in 16 highly VL endemic foci in Muzaffarpur district in Bihar. Household and individual information was gathered and capillary blood samples were collected on filter papers. Direct agglutination test (DAT) was used to determine infected individuals (cut-off titre 1:1600). DAT results were tabulated against individual and household variables. A multivariate generalized estimating equation (GEE) model was used to study the prevalence of serologically positive individuals taking into account the clustering at household and cluster levels. RESULTS: Of study subjects 18% were DAT positive, and this proportion increased with age. Women had a significantly lower prevalence than men >14 years old. Owning domestic animals (cows, buffaloes or goats) was associated with a higher risk of being DAT positive [OR 1.16 (95% CI 1.01-1.32)], but socio-economic status was not. CONCLUSIONS: Prevalence of leishmanial antibodies was high in these communities, but variable. Demographic factors (i.e. marriage) may explain the lower DAT positivity in women >14 years of age. Within these homogeneously poor communities, socio-economic status was not linked to L. donovani infection risk at the individual level, but ownership of domestic animals was

Eflornithine is a cost-effective alternative to melarsoprol for the treatment of second-stage human West African trypanosomiasis in Caxito, Angola.

OBJECTIVE: To compare the cost-effectiveness of eflornithine and melarsoprol in the treatment of human African trypanosomiasis. METHOD: We used data from a Médecins Sans Frontières treatment project in Caxito, Angola to do a formal cost-effectiveness analysis, comparing the efficiency of an eflornithine-based approach with melarsoprol. Endpoints calculated were: cost per death avoided; incremental cost per additional life saved; cost per years of life lost (YLL) averted; incremental cost per YLL averted. Sensitivity analysis was done for all parameters for which uncertainty existed over the plausible range. We did an analysis with and without cost of trypanocidal drugs included. RESULTS: Effectiveness was 95.6% for melarsoprol and 98.7% for eflornithine. Cost/patient was 504.6 for melarsoprol and 552.3 for eflornithine, cost per life saved was 527.5 USD for melarsoprol and 559.8 USD for eflornithine without cost of trypanocidal drugs but it increases to 600.4 USD and 844.6 USD per patient saved and 627.6 USD and 856.1 USD per life saved when cost of trypanocidal drugs are included. Incremental cost-effectiveness ratio is 1596 USD per additional life saved and 58 USD per additional life year saved in the baseline scenario without cost of trypanocidal drugs but it increases to 8169 USD per additional life saved and 299 USD per additional life year saved if costs of trypanocidal drugs are included. CONCLUSION: Eflornithine saves more lives than melarsoprol, but melarsoprol is slightly more cost-effective. Switching from melarsoprol to eflornithine can be considered as a cost-effective option according to the WHO choice criteria

Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial

OBJECTIVES: To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions. METHODS: Randomized, multi-centre, open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso: one arm with use of RDT before treatment decision, one arm managed clinically. Primary endpoint: persistence of fever at day 4. Secondary endpoints: frequency of malaria treatment and of antibiotic treatment. RESULTS: A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season, and randomized either to be submitted to RDT (P_RTD) or to be managed presumptively (P_CLIN). In both seasons, no significant difference was found between the two randomized groups in the frequency of antimalarial treatment, nor of antibiotic prescription. In the dry season, 80.8% and 79.8% of patients with a negative RDT were nevertheless diagnosed and treated for malaria, and so were 85.0% and 82.6% negative patients in the rainy season. In the rainy season only, both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9%, P = 0.00 and 0.00, respectively). CONCLUSION: Our study was inconclusive on RDT safety (clinical outcome in the two randomized groups), because of an exceedingly and unexpectedly low compliance with the negative test result. Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current, presumptive treatment strategy