Summary Objective To analyse the outcomes of antiretroviral therapy (ART) in routine conditions in a rural hospital in the Far‐North province of Cameroon. Method Retrospective cohort study of 1187 patients >15 years who started ART between July 2001 and December 2006. The survival time was estimated by Kaplan–Meier analysis and Cox proportional hazard models were fitted to explain survival. Results Upon enrolment, 90.4% patients were in WHO stage III or IV and 56.1% had a BMI <18.5. Median CD4 count was 105 cells/mm³ (IQR 40–173). At the end of the study period, 338/1187 had died and 59/1187 were lost to follow‐up. The survival probability was 77% at 1 year [95% CI: 75–80] and 47% at 5 years [95% CI: 40–55]. The median survival time was 58 months. CD4 count, haemoglobin, BMI, sex and clinical stage at enrolment were independent predictors of mortality. Conclusion This study confirms the clinical benefit of ART programs in a remote and resource‐constrained setting operating in routine conditions. The challenge ahead is to secure earlier access to ART and to maintain its longer‐term benefit.
HIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites. The additional malaria parasite biomass related to HIV-1 co-infection in sub-Saharan Africa was estimated by a mathematical model. Parasite biomass was computed as the incidence rate of clinical malaria episodes multiplied by the number of parasites circulating in the peripheral blood of patients at the time symptoms appear. A mathematical model estimated the influence of HIV-1 infection on parasite density in clinical malaria by country and by age group, malaria transmission intensity and urban/rural area. In a multivariate sensitivity analysis, 95% confidence intervals (CIs) were calculated using the Monte Carlo simulation. The model shows that in 2005 HIV-1 increased the overall malaria parasite biomass by 18.0% (95%CI: 11.6–26.9). The largest relative increase (134.9–243.9%) was found in southern Africa where HIV-1 prevalence is the highest and malaria transmission unstable. The largest absolute increase was found in Zambia, Malawi, the Central African Republic and Mozambique, where both malaria and HIV are highly endemic. A univariate sensitivity analysis shows that estimates are sensitive to the magnitude of the impact of HIV-1 infection on the malaria incidence rates and associated parasite densities. The HIV-1 epidemic by increasing the malaria parasite biomass in sub-Saharan Africa may also increase the emergence of antimalarial drug resistance, potentially affecting the health of the whole population in countries endemic for both HIV-1 and malaria.
Malaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs) are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern. Cross-sectional study. Subjects: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. Exclusion criteria: severe clinical condition needing urgent care. In the dry season, 186/852 patients with fever (22%) and 213/1,382 patients without fever (15%) had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64%) and 623/1,669 (37%), respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV) was 9% and the negative predictive value (NPV) was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for adults to 82% for infants, while the NPV ranged from 84% for infants to over 99% for adults. In the dry season the RDT has a low positive predictive value, but a very high negative predictive value for malaria-attributable fever. In the rainy season the negative test safely excludes malaria in adults but not in children.
Summary Background Mortality caused by tetanus is still a serious health problem in developing countries. Apart from immunization, early treatment with equine antitetanus serum (ATS) or human tetanus immunoglobulin (TIG) is the real treatment that can avoid death. On pathophysiological grounds intrathecal administration would be preferred because of high concentrations of the antiserum in cerebrospinal fluid and thus around the nerve roots. Many studies concluded on its effectiveness whereas others did not find any superiority of this method. However, most of those studies were not random and/or had no sufficient weight. Objective To assess the efficacy of intrathecal therapy with ATS in neonates and adults. Methods Meta‐analysis: Clinical trials were identified by searching Medline, the Cochrane library and Current Contents. Published randomized studies in English or French comparing intrathecal therapy and intramuscular therapy (IMS) were analysed with Revman, R, and Stata software. Treatment effects were evaluated by relative risk (RR) between intrathecal vs. intramuscular administration. Results A total of 942 patients were included in 12 trials, 484 in the intrathecal group and 458 in the intramuscular one. The combined RR of mortality for intrathecal vs. IMS was 0.71 (95% CI, 0.62–0.81). The superiority of intrathecal therapy also emerged when the analysis was performed in subcategories of both adults and neonates and for high and low dose of intrathecal serotherapy. Conclusion Intrathecal administration of ATS or TIG is more beneficial than intramuscular administration in the treatment of tetanus.
e19564 Background: Transdermal buprenorphine has also proven effect on neuropathic pain and is of interest for the management of pain in palliative cancer patients. An expert panel found that the use of higher doses than those recommended in the prescribing information may be warranted though there is insufficient evidence. The need and value of high dose buprenorphine are assessed. Methods: Prospective observational study. Patients attending the department of oncology and/or the department palliative care who suffer pain and would normally be offered transdermal treatment with buprenorfine. 36 patients were given full information and asked to sign informed consent. The primary outcome parameter was the patient’s report of pain intensity, and side effects. Where possible the need for breakthrough medication was documented. Results: 36 patients signed the informed consent. 5 patients never started buprenorfine treatment and 3 patients stopped immediately after the first application of the patch. 28 patients received buprenorfine for at least 3 days. Pain control was achieved in 21 out of 28 evaluable patients. In two patients, the dose was increased to 210 and 175 µg/hr. Two patients were switched to fentanyl TDD when the 140 µg/hr dose buprenorfine did not provide a satisfactory outcome. Transdermal buprenorfine is an efficient analgesic achieving adequate pain control in the majority of patients. In this observational prospective study that represents daily practice, 1/7 patients required doses higher than 140 µg/h. 36 patients signed the informed consent. 5 Patients never started buprenorfine treatment and 3 patients stopped immediately after the first application of the patch. 28 patients received buprenorfine for at least 3 days. Pain control was achieved in 21 out of 28 evaluable patients. In two patients, the dose was increased to 210 and 175 µg/hr. Two patients were switched to fentanyl TDD when the 140 µg/hr dose buprenorfine did not provide a satisfactory outcome. Conclusions: Transdermal buprenorfine is an efficient analgesic achieving adequate pain control in the majority of patients. In this observational prospective study that represents daily practice, 1/7 patients required doses higher than 140 µg/h.
Summary Objective The direct agglutination test (DAT) for visceral leishmaniasis (VL) with liquid (LQ) antigen is known to be only moderately reproducible because of inter‐observer and batch‐to‐batch variability as well as its sensitivity to temperature and shaking during transport. We evaluated a DAT with freeze‐dried (FD) antigen and compared it with the LQ antigen version. Methods Blood samples of clinical VL suspects and healthy endemic controls were collected in Sudan, Nepal and India. Both test versions were performed in duplicate in the respective countries and in the reference laboratory. Interbatch variability and stability tests were conducted and agreement was examined within and between centres on a dichotomic scale by Cohen's kappa as well as on a continuous scale through Bland–Altman plots. Results The FD antigen remains fully active even after storage at 45 °C for 24 months. Using a cut‐off titre of 1 : 6400, the agreement between the FD and the LQ formats was excellent. Conclusion The major advantages of FD antigen are its better stability at higher temperatures and its longer shelf life, which make it much more suitable than the LQ version for use in the field.
Abstract Objectives Diagnosis of the neurological stage of human African trypanosomiasis is performed by examination of cerebrospinal fluid ( CSF ) for the presence of trypanosomes and numbers of white blood cells ( WBC ). Both CSF parameters are also used to assess treatment outcome during follow‐up. In view of the importance of CSF examination, and the practical problems encountered with it, we compared the sensitivity of two trypanosome concentration techniques and the repeatability of two cell counting methods, as well as occurrence of systematic differences between them. Methods Patients were recruited at Dipumba hospital, in Mbuji‐Mayi in the Democratic Republic of the Congo. In 94 CSF samples, trypanosome detection was performed with modified single centrifugation ( MSC ) and double centrifugation ( DC ). On 189 CSF samples with ≤30 cells/μl, cell counting was performed in duplicate in a Fuchs–Rosenthal counting chamber and in a disposable Uriglass counting chamber. Results Modified single centrifugation detected trypanosomes in significantly ( P < 0.0001) more patients (85) than DC (46). Cell counts did not differ systematically in the two methods. Variability in the differences between duplicate cell counts was significantly higher ( P = 0.002) in Uriglass ( SD of differences 2.03) than in Fuchs–Rosenthal ( SD of differences 1.62). Conclusions For analysis of CSF in the context of sleeping sickness stage determination and follow‐up after treatment, we strongly recommend the MSC for parasite detection and the application of disposable counting chambers. When the first cell count is ≤20 cells/μl, we recommend repeating the counting procedure on the same CSF specimen and taking the average of both countings.
We evaluated Families Matter! Program (FMP), an intervention designed to improve parent-child communication about sexual risk reduction and parenting skills. Parents of 10- to 12-year-olds were recruited in western Kenya. We aimed to assess community acceptability and FMP's effect on parenting practices and effective parent-child communication. Data were collected from parents and their children at baseline and 1 year postintervention. The intervention's effect was measured on six parenting and parent-child communication composite scores reported separately for parents and children. Of 375 parents, 351 (94%) attended all five intervention sessions. Parents' attitudes regarding sexuality education changed positively. Five of the six composite parenting scores reported by parents, and six of six reported by children, increased significantly at 1 year postintervention. Through careful adaptation of this U.S. intervention, FMP was well accepted in rural Kenya and enhanced parenting skills and parent-child sexuality communication. Parents are in a unique position to deliver primary prevention to youth before their sexual debut as shown in this Kenyan program.
Research is ongoing to develop multipurpose vaginal rings to be used continuously for contraception and to prevent Human Immunodeficiency Virus (HIV) infection. Contraceptive vaginal rings (CVRs) are available in a number of countries and are most of the time used intermittently i.e. three weeks out of a 4-week cycle. Efficacy trials with a dapivirine-containing vaginal ring for HIV prevention are ongoing and plans to develop multi-purpose vaginal rings for prevention of both HIV and pregnancy have been elaborated. In contrast with the CVRs, multi-purpose vaginal rings will have to be used continuously. Women who continuously use a CVR will no longer have menses. Furthermore, some safety aspects of CVR use have never been studied in-depth in the past, such as the impact of the vaginal ring on the vaginal microbiota, biofilm formation and induction of inflammation. We studied acceptability and these novel aspects of safety in Rwandan women. Although significant progress has been made over the past decade, Rwanda still has a high unmet need for contraception (with 47% unplanned births) and a generalized HIV epidemic, and CVRs are not yet available.