bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twenty‐four‐week safety and tolerability of nevirapine vs. abacavir in combination with zidovudine/lamivudine as first‐line antiretroviral therapy: a randomized double‐blind trial (NORA)*
Authors:   Dart Trial Team
Published: August 2010

SummaryObjective  To compare the safety/tolerability of abacavir and nevirapine in HIV‐infected adults starting antiretroviral (ARV) therapy in Uganda.Methods  Twenty‐four‐week randomized double‐blind trial conducted with 600 symptomatic ARV‐naive adults with CD4 <200 cells/mm3 allocated to zidovudine/lamivudine plus 300 mg abacavir (A) and nevirapine placebo (n = 300) or 200 mg nevirapine (N) and abacavir placebo (n = 300) twice daily. The primary endpoint was any serious adverse event (SAE) definitely/probably or uncertain whether related to blinded nevirapine/abacavir. Secondary endpoints were adverse events leading to permanent discontinuation of blinded nevirapine/abacavir, and grade 4 events.Results  Seventy‐two per cent participants were women; 19% had WHO stage 4 disease; the median age was 37 years (range 18–66); the median baseline CD4 count was 99 cells/mm3 (1–199). Ninety‐five per cent completed 24 weeks: 4% died and 1% were lost to follow‐up. Thirty‐seven SAEs occurred on blinded drug in 36 participants. Twenty events [6 (2.0%) abacavir, 14 (4.7%) nevirapine participants] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [HR = 0.42 (95% CI 0.16–1.09) P = 0.06]. Only 2.0% of abacavir participants [six patients (0.7–4.3%)] experienced a suspected hypersensitivity reaction (HSR). In total 14 (4.7%) abacavir and 30 (10.0%) nevirapine participants discontinued blinded abacavir/nevirapine (P = 0.02): because of toxicity (6A, 15N; P = 0.07, all rash/possible HSR and/or hepatotoxicity), anti‐tuberculosis therapy (6A, 13N), or for other reasons (2A, 2N).Conclusions  There was a trend towards a lower rate of serious adverse reactions in Ugandan adults with low CD4 starting ARV regimens with abacavir than with nevirapine. This suggests that abacavir could be used more widely in resource‐limited settings without major safety concerns.
Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?
Authors: Nebie I. , Tiono A. B. , Diallo D. A. , Samandoulougou S. , Diarra A. , Konate A. T. , Cuzin‐Ouattara N. , Theisen M. , Corradin G. , Cousens S. , Ouattara A. S. , Ilboudo‐Sanogo E. , Sirima B. S. 
Published: August 2010

SummaryObjectives  To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)5 GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria.Methods  Cross‐sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria.Results  Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non‐responders [(NANP)5 (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46–0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48–0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50–1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32–0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38–1.05; P = 0.08).Conclusion  Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.
Chloroquine‐resistance molecular markers (Pfcrt T76 and Pfmdr‐1 Y86) and amodiaquine resistance in Burkina Faso
Authors: Tinto Halidou , Guekoun Lougué , Zongo Issaka , Guiguemdé Robert Tinga , D’Alessandro Umberto , Ouédraogo Jean Bosco 
Published: August 2010

SummaryWe investigated the relationship between the two main molecular markers for chloroquine resistance (Pfcrt T76 and Pfmdr‐1 Y86) and the clinical efficacy of amodiaquine in Burkina Faso. Before treatment, the prevalence of Pfcrt T76, Pfmdr‐1 Y86 or both mutations in the same infection was significantly higher in patients who experienced a recrudescence than in those who successfully responded to the treatment. Therefore, these two molecular markers could be useful in monitoring amodiaquine resistance, particularly in countries where this drug is used in combination with artesunate as first‐ or second‐line treatment.
A simple approach to test for interaction between intervention and an individual‐level variable in community randomized trials
Authors: Cheung Yin Bun , Jeffries David , Thomson Andrew , Milligan Paul 
Published: August 2010

SummaryObjective  To develop a simple and robust approach for the test of interaction between community intervention and an individual‐level variable suitable for use in typical situations of community randomized trials (CRTs), i.e. small number of communities but large number of subjects per community.Methods  We propose a method based on taking the difference between summary statistics from groups of individuals with and without an attribute within each community, then applying a two‐sample t‐test or Wilcoxon test to compare the distribution of within‐community differences between trial arms. The method is evaluated using simulations and illustrated using data from a CRT of a health education intervention. Approximate sample size formulas are derived.Results  Analyses based on the t‐test give power very close to expected level in a variety of situations, including when the summary statistics are not symmetrically distributed across communities, the covariate is not distributed as planned, and the number of communities per intervention arm ranges from 8 to 20. Even in the situation with as few as four communities per arm, the power is only slightly lower than expected. Type I error rates always closely follow 5% as required, whether the distributional assumption is correct or not. The application of the Wilcoxon test appears too conservative.Conclusions  The proposed approach to test for interaction is valid and easy to use. The application of the t‐test in this setting is robust.
Validity of non‐invasive assessment of anaemia in pregnancy
Authors: Bergsjø Per , Evjen‐Olsen Bjørg , Hinderaker Sven Gudmund , OleKing’ori Naphtal , Klepp Knut‐Inge 
Published: August 2010

SummaryObjective  To test the accuracy of clinical symptoms and signs for anaemia in pregnant women, as assessed by nurse‐midwives, in two locations in Northern Tanzania.Methods  One location was at 1000 m above sea level, the other at 1800 m. Midwives performed examinations and conducted structured interviews to detect severe anaemia at the first antenatal care visit before haemoglobin (hb) results were revealed; 369 and 535 women of all parities were examined in consecutive order at the two locations. Severe anaemia was defined as hb <75 g/l in the first and <80 g/l in the second (higher) location, based on altitude effect on hb distributions.Results  Hb distribution differed substantially between the two locations, with much higher hb levels among those living at 1800 m. Sensitivities for detection of severe anaemia based on individual signs (pallor, conjunctiva, etc.) were 0.85, but only 0.33 to 0.44 for those living at lower and for those at higher altitudes, respectively. Conversely, specificities were around 0.90 at higher and 0.55 at lower altitudes, respectively. Symptoms (headache, dizziness, palpitations, etc.) were too common among those without anaemia to be useful as distinguishing features. Changing the definition of severe anaemia to higher cut‐off hb values did not materially alter the results.Conclusion  Validity of non‐invasive tests to detect severe anaemia in pregnant women varies by locality. In a high‐altitude area detection rate was low (sensitivity around 40%). In lower‐lying areas detection rate was high, at the cost of low specificity (around 45% false positive tests). Symptoms like headache, dizziness and fatigue were too common to discriminate those with severe anaemia.
Relapses vs. reactions in multibacillary leprosy: proposal of new relapse criteria
Authors: Linder Katharina , Zia Mutaher , Kern Winfried V. , Pfau Ruth K. M. , Wagner Dirk 
Published: August 2010

SummaryObjectives  To compare a new scoring system for multibacillary (MB) leprosy relapses, which combines time factor, risk factors and clinical presentation at relapse, to WHO criteria.Methods  Data were collected on all relapses diagnosed between 1998 and 2004 at the Marie‐Adelaide‐Centre in Karachi, Pakistan, including case histories, clinical manifestations, follow‐up, bacterial indices, treatment and contacts. For the diagnosis of MB relapses a simple scoring system was developed and validated on a data‐set of mouse foot pads (MFP)‐confirmed relapses (Leprosy Reviews, 76, 2005, 241). Its sensitivity was further evaluated in the Karachi relapse cohort. The P‐value was calculated with McNemar’s test with continuity correction.Results  The new scoring system that combines time factor, risk factors and clinical presentation at relapse had a higher sensitivity in MFP‐confirmed relapses than the WHO‐criteria (95%vs. 65%, P < 0.01). The sensitivity of the scoring system was also significantly higher than the WHO criteria in the 57 cases of MB‐relapses diagnosed in Karachi (72%vs. 54%, P < 0.05).Conclusions  This new simple scoring system for diagnosing MB‐relapses in leprosy should be further validated in a prospective study to confirm its superior sensitivity and to evaluate the specificity of these criteria by using MFP‐confirmation for patients presenting with signs of activity after treatment.
Diversity of risk of mother‐to‐child HIV‐1 transmission according to feeding practices, CD4 cell count, and haemoglobin concentration in a South African cohort
Authors: Tournoud M. , Ecochard R. , Kuhn L. , Coutsoudis A. 
Published: August 2010

SummaryObjective  To estimate the probabilities of intrapartum and postpartum HIV‐1 mother‐to‐child‐transmission according to various feeding practices (formula feeding, exclusive breastfeeding, or mixed‐feeding) and to other mother and infant covariates.Methods  We used the promotion time model extended to multiple exposures to study the probability of infection attributable to each transmission occasion. Blood samples from 551 infants from Durban (South Africa) born to HIV‐1 positive untreated mothers between 1995 and 1998 were sequentially tested until 15 months.Results  The probability of infection attributable to in utero and intrapartum transmission was 21.88% (18.71–25.20) and was not significantly associated with the feeding practice. The probability of infection attributable to postnatal transmission through exclusive breastfeeding was negligible −0.7% (0–2.5) for 6 months of exclusive breastfeeding‐‐ in comparison with that observed with mixed‐feeding −6.15% (3.16–9.57) for 6 months of mixed‐feeding. Maternal CD4 cell count and gestational age were significant predictors of intrapartum transmission probability while maternal CD4 cell count and maternal haemoglobin concentration were significant predictors of postpartum transmission probability.Conclusion  Decisions about appropriate infant feeding practices should take into account the difference in postpartum transmission risk between exclusive and mixed‐feeding. Mixed‐feeding should be all the more avoided that mothers have poor immunological statuses and low haemoglobin concentrations.
Nutritional status and common infections in infants in Burkina Faso: interest of an ‘overall morbidity score’
Authors: Prosper Sawadogo S. , Martin‐Prével Yves , Capon Gilles , Traoré S. Alfred , Delpeuch Francis 
Published: August 2010

SummaryObjective  To study the overall impact of morbidity on the nutritional status of infants in a rural area of Burkina‐Faso.Method  A cohort of children (n = 114) were monitored from age 6 months to 2 years in 30 villages in north‐eastern Burkina Faso. Anthropometric measurements and the incidence of illness were recorded at 6, 9, 12, 15, 18 and 24 months. An overall morbidity score was constructed including the duration of common illnesses and their effect on appetite. Mixed linear regression models were used to analyse the relation between this score and both the weight‐for‐length (WFL) and the length‐for‐age (LFA) index.Results  After adjustment for potential confounders, the morbidity score at time T was strongly correlated with the WFL index at time T (P < 0.0001) and weakly correlated with the LFA index at time T + 1 (P = 0.06). When the morbidity score was divided into classes, at time T the mean WFL z‐score for children with a high morbidity score was 0.34 z‐scores lower than the one for healthy children (P < 0.0001); at time T + 1, the difference in the mean LFA z‐scores between the same groups was 0.09 z‐score (P = 0.02). However, similar results were obtained using simpler expressions of morbidity. Taken separately, diarrhoea or febrile illness had an effect on WFL (at time T), but only diarrhoea had an effect on LFA (at time T + 1).Conclusion  Morbidity was strongly correlated with weight loss in children in the short term and weakly correlated with a slowdown in growth.
Assessing the validity of health facility‐based data on insecticide‐treated bednet possession and use: comparison of data collected via health facility and household surveys – Lindi region and Rufiji district, Tanzania, 2005
Authors: Skarbinski Jacek , Winston Carla A. , Massaga Julius J. , Kachur S. Patrick , Rowe Alexander K. 
Published: August 2010

SummaryObjective  To assess the validity of health facility (HF)‐based data on bednet and insecticide‐treated bednet possession and use by children <5 years old.Methods  We compared estimates based on data collected via HF surveys of under‐5s attending well‐child visits (e.g. immunizations) and sick‐child visits vs. representative household surveys (a ‘gold standard’ method for measuring insecticide‐treated net coverage). In Lindi region, Tanzania, we collected contemporaneous data on 637 under‐5s via a HF survey (444 well‐child visits and 193 sick‐child visits), and on 305 households with an under‐5 (including 354 children) via a household survey. In Rufiji district, Tanzania, we collected contemporaneous data on 1433 under‐5s via a HF survey (911 well‐child visits and 522 sick‐child visits), and on 328 households with an under‐5 (including 455 children) via a household survey.Results  Possession of bednets by households with an under‐5 was similar using HF data and household data in both Lindi region and Rufiji district. However, reported use of bednets was significantly higher in HF data than household data in both Lindi and Rufiji, as was reported use of insecticide‐treated bednets. HF‐based data accurately estimated community‐level bednet possession in households with an under‐5, but overestimated community‐level bednet use by 9–35% and insecticide‐treated bednet use by 15–21%.Conclusions  Information bias rather than selection bias appears to be a key cause for the overestimation of bednet and insecticide‐treated bednet use (e.g. social desirability bias: caretakers of under‐5s attending health facilities might be more likely to report using bednets and insecticide‐treated bednets). Additional studies of the validity, cost and utility of HF‐based data to monitor insecticide‐treated bednet use are needed before recommending this monitoring strategy for widespread use. Overestimating insecticide‐treated bednet use could lead to inappropriate public health actions and missed opportunities for achieving local and global public health goals.
Clinical diagnosis of malaria and the risk of chloroquine self‐medication in rural health centres in Burkina Faso
Authors: Pfeiffer K. , Some F. , Müller O. , Sie A. , Kouyaté B. , Haefeli W. E. , Zoungrana A. , Gustafsson L. L. , Tomson G. , Sauerborn R. 
Published: August 2010

SummaryObjective  To assess the quality of healthcare workers’ performance with regard to malaria diagnosis and treatment and to assess patients’ self‐medication with chloroquine (CQ) before and after presentation at a health centre.Methods  In the rainy season 2004, in five rural dispensaries in Burkina Faso, we observed 1101 general outpatient consultations and re‐examined all these patients. CQ whole blood concentrations of confirmed malaria cases were measured before and after treatment.Results  The clinical diagnosis based on fever and/or a history of fever had a sensitivity of 75% and a specificity of 41% when compared to confirmed malaria (defined as an axillary temperature of ≥37.5 °C and/or a history of fever and parasites of any density in the blood smear). Few febrile children under 5 years of age were assessed for other diseases than malaria such as pneumonia. No antimalarial was prescribed for 1.3% of patients with the clinical diagnosis malaria and for 24% of confirmed cases, while 2% received an antimalarial drug prescription without the corresponding clinical diagnosis. CQ was overdosed in 22% of the prescriptions. Before and 2 weeks after consultation, 25% and 46% respectively of the patients with confirmed malaria had potentially toxic CQ concentrations.Conclusion  As long as artemisinin‐based combination therapy remains unavailable or unaffordable for most people in rural areas of Burkina Faso, self‐medication with and prescription of CQ are likely to continue despite increasing resistance. Apart from considering more pragmatic first‐line regimens for malaria treatment such as the combination of sulfadoxine‐pyrimethamine with amodiaquine, more and better training on careful clinical management of febrile children including an appropriate consideration of other illnesses than malaria should be made available in the frame of the IMCI initiative in sub‐Saharan Africa.
Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case–control study
Authors: Lee Ellen Hyun‐Ju , Lewis Rosamund F. , Makumbi Issa , Kekitiinwa Adeodata , Ediamu Tom D. , Bazibu Monic , Braka Fiona , Flannery Brendan , Zuber Patrick L. , Feikin Daniel R. 
Published: August 2010

SummaryObjective  To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda.Methods  Case–control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case‐patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables.Results  We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV‐negative, had received ≥2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92–100%] and 96% (95% CI 80–100%) when cases were compared with neighbourhood and hospital controls, respectively.Conclusion  In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality.
The long‐term social and economic impact of HIV on the spouses of infected individuals in northern Malawi
Authors: Floyd Sian , Crampin Amelia C. , Glynn Judith R. , Mwenebabu Michael , Mnkhondia Stancelaus , Ngwira Bagrey , Zaba Basia , Fine Paul E. M. 
Published: August 2010

SummaryObjective  To assess the social and economic impact of HIV‐related illness and death on the spouses of HIV‐infected individuals.Methods  From population‐based surveys in the 1980s in Karonga district, northern Malawi, 197 ‘index individuals’ were identified as HIV‐positive. A total of 396 HIV‐negative ‘index individuals’ were selected as a comparison group. These individuals, and their spouses and children, were followed up in 1998–2000, in a retrospective cohort study. All analyses compared spouses of HIV‐positive indexes with those of HIV‐negative indexes.Results  By 1998–2000, most marriages involving an HIV‐positive index individual had ended in widowhood. Twenty‐Six percent of the wives of HIV‐positive index men experienced household dissolution precipitated by widowhood, compared with 5% of the wives of HIV‐negative index men. Corresponding percentages for husbands of index women were 14% and 1%. Widow inheritance was uncommon. The remarriage rate among separated or widowed wives of HIV‐positive index men was half that of such wives of HIV‐negative index men. About 30% of surviving wives of HIV‐positive index men were household heads at the time of follow‐up, compared with 5% of such wives of HIV‐negative index men. Almost all these women were widows who lost their husband when >35 years old, and they had relatively few household assets.Conclusions  The social and economic impact of HIV on the spouses of HIV‐infected individuals in rural northern Malawi is substantial. Interventions that strengthen society’s ability to absorb and support widows and widowers, and their dependents, without necessarily involving the traditional coping mechanism of remarriage, are essential.
The effect of user fees on prescribing quality in rural Nepal: two controlled pre‐post studies to compare a fee per drug unit vs. a fee per drug item
Authors: Holloway Kathleen A. , Karkee Shiva , Tamang Ashalal , Gurung Yam Bahadur , Pradhan Ramesh , Reeves Barnaby C. 
Published: August 2010

SummaryObjective  To compare prescribing quality with a fee per drug unit vs. a fee per drug item.Methods  Prescribing data were collected prospectively over 10 years from 21 health facilities in two districts of rural eastern Nepal. In 1995, both districts charged a fee per drug item. By 2000, one district was charging a fee per drug unit, and the second district continued to charge a fee per drug item (control group). By 2002, the second district was also charging a fee per drug unit. These fee changes allowed two pre‐post ‘cohort’ with control analyses to compare INRUD/WHO drug use indicators for a fee per drug unit vs. a fee per drug item.Results  Charging a fee per drug unit increased the percentage of antibiotics prescribed in under‐dosage by 11–12% (P = 0.02 and 0.02), decreased the percentage of patients prescribed injections by 4–6% (P = 0.002 and 0.02), reduced the units per drug item prescribed by 1.7 (P = 0.02 and 0.03), and decreased compliance with standard treatment guidelines by 11–15% (P = 0.02 and 0.06).Conclusion  A fee per unit was associated with prescription of fewer units of drugs and fewer expensive drugs (such as injections), resulting in significantly poorer compliance with standard treatment guidelines. This finding is of great concern for public health in countries where patients are charged a fee per unit of drug.