bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for HIV/AIDS in a low HIV prevalence site of sub‐Saharan Africa
Authors: Croce Francesco , Fedeli Paolo , Dahoma Mohamed , Dehò Lorenzo , Ramsan Mahdi , Adorni Fulvio , Corvasce Stefano , Galli Massimo
Published: August 2010

We conducted a hospital‐based survey on prevalence and risk factors of HIV‐1/2 and other viral infections in Zanzibar archipelago. Blood samples, socio‐demographic and behavioural data were collected from 2697 patients. The overall HIV prevalence was 2.9%. About 1.4%, 2.1%, 4.2% of antenatal clinic (ANC) attendees and 2.1%, 3.7%, 5.3% of blood donors were, respectively, HIV‐Abs‐, HTLV‐Abs‐ and HBs‐Ag‐positive; 5.5% of blood donors were HCV‐affected. Co‐infections were rare. Exactly 3.4% of the children aged 6–10 years were HIV‐positive. People aged 26–35 years [adjusted odds ratio (AOR) 4.4, 95% CI (confidence interval) 1.72–11.22; P = 0.002], illiterate subjects (AOR 3.6, 95% CI 1.65–7.98; P = 0.001) mobile workers (AOR 7.0, 95% CI 1.41–34.62; P = 0.02) and previously operated patients (AOR 1.9, 95% CI 1.02–3.66; P = 0.04) were at higher risk for HIV/AIDS. Any of the examined factors were associated with hepatitis B virus, hepatitis C virus and human T lymphotropic virus type 1/2 transmission. HIV/AIDS prevention strategies must primarily be addressed to traditional high‐risk groups and secondarily to unsafe health care procedures in relatively preserved sub‐Saharan areas.
A quantitative ultrastructural study of renal pathology in fatalPlasmodium falciparummalaria
Authors: Nguansangiam Sudarat , Day Nicholas P. J. , Hien Tran Tinh , Mai Nguyen Thi Hoang , Chaisri Urai , Riganti Mario , Dondorp Arjen M. , Lee Sue J. , Phu Nguyen Hoan , Turner Gareth D. H. , White Nicholas J. , Ferguson David J. P. , Pongponratn Emsri
Published: August 2010

Objective To use electron microscopy to examine the role of parasitized red blood cell (PRBC) sequestration in the pathogenesis of acute renal failure in severe falciparum malaria.

Methods Ultrastructural pathological examination of renal tissues from Southeast Asian adults (n = 63) who died from severe falciparum malaria. Qualitative and quantitative determination of the major pathological features of disease, including PRBC and leukocyte sequestration. Clinico‐pathological correlation with the pre‐mortem clinical picture and peripheral parasite count.

Results There was a high incidence of malaria‐associated renal failure in this population (> 40%) and a correlation between this incidence, severe malarial anaemia and shock. Pathological features included PRBC sequestration in glomerular and tubulo‐interstitial vessels, acute tubular damage and mild glomerular hypercellularity resulting from the accumulation of host monocytes within glomerular capillaries. No evidence for an immune complex mediated glomerulonephritis was found. There was a correlation between parasite sequestration in the kidney and pre‐mortem renal failure, although overall levels of sequestration were relatively low. Levels of sequestration (Knob+ PRBC) were significantly higher in malaria‐associated renal failure than in fatal cases without renal failure (P = 0.005).

Conclusion Malaria‐associated renal failure is a common and serious complication of severePlasmodium falciparummalaria in this population, associated with acute tubular injury rather than glomerulonephritis, and linked to localization of host monocytes in the kidney as well as sequestration of PRBCs.
Efficacy of pyrethroid‐treated nets against malaria vectors and nuisance‐biting mosquitoes in Tanzania in areas with long‐term insecticide‐treated net use
Authors: Kulkarni Manisha A. , Malima Robert , Mosha Frank W. , Msangi Shandala , Mrema Ezra , Kabula Bilali , Lawrence Boniface , Kinung’hi Safari , Swilla John , Kisinza William , Rau Manfred E. , Miller Jane E. , Schellenberg Joanna Armstrong , Maxwell Caroline , Rowland Mark , Magesa Stephen , Drakeley Chris
Published: August 2010

Objective  To measure pyrethroid susceptibility in populations of malaria vectors and nuisance‐biting mosquitoes in Tanzania and to test the biological efficacy of current insecticide formulations used for net treatment.

Methods  Anopheles gambiae Giles s.l., An. funestus Giles s.l. and Culex quinquefasciatus Say were collected during three national surveys and two insecticide‐treated net (ITN) studies in Tanzania. Knockdown effect and mortality were measured in standard WHO susceptibility tests and ball‐frame bio‐efficacy tests. Test results from 1999 to 2004 were compared to determine trends in resistance development.

Results  Anopheles gambiae s.l. and An. funestus s.l. were highly susceptible to permethrin (range 87–100%) and deltamethrin (consistently 100%) in WHO tests in 1999 and 2004, while Culex quinquefasciatus susceptibility to these pyrethroids was much lower (range 7–100% and 0–84% respectively). Efficacy of pyrethroid‐treated nets was similarly high against An. gambiae s.l. and An. funestus s.l. (range 82–100%) while efficacy against Cx. quinquefasciatus was considerably lower (range 2–100%). There was no indication of development of resistance in populations of An. gambiae s.l. or An. funestus s.l. where ITNs have been extensively used; however, susceptibility of nuisance‐biting Cx. quinquefasciatus mosquitoes declined in some areas between 1999 and 2004.

Conclusion  The sustained pyrethroid susceptibility of malaria vectors in Tanzania is encouraging for successful malaria control with ITNs. Continued monitoring is essential to ensure early resistance detection, particularly in areas with heavy agricultural or public health use of insecticides where resistance is likely to develop. Widespread low susceptibility of nuisance‐biting Culex mosquitoes to ITNs raises concern for user acceptance of nets.
Cost‐effectiveness of annual targeted larviciding campaigns in Cambodia against the dengue vector Aedes aegypti
Authors: Suaya Jose A. , Shepard Donald S. , Chang Moh‐Seng , Caram Mariana , Hoyer Stefan , Socheat Duong , Chantha Ngan , Nathan Michael B.
Published: August 2010

Objective  To assess the cost‐effectiveness (CE) of annual targeted larviciding campaigns from 2001 to 2005 against the dengue vector Aedes aegypti in two urban areas of Cambodia with a population of 2.9 million people.

Methods  The intervention under analysis consisted of annual larviciding campaigns targeting medium to large water storage containers in households and other premises. The CE compared the intervention against the hypothetical alternative of no intervention. The CE was calculated as the ratio of disability adjusted life years (DALYs) saved to the net cost of the intervention (in 2005 US dollars) by year. A sensitivity analysis explored the range of study parameters.

Results  The intervention reduced the number of dengue cases and deaths by 53%. It averted an annual average of 2980 dengue hospitalizations, 11 921 dengue ambulatory cases and 23 dengue deaths, resulting in a saving of 997 DALYs per year. The gross cost of the intervention was US$ 567 800 per year, or US$ 0.20 per person covered. As the intervention averted considerable medical care, the annual net cost of the intervention was US$ 312 214 (US$ 0.11 per person covered) from a public sector perspective and US$ 37 137 (US$ 0.01 per person covered) from a societal perspective. The resulting CE ratios were: US$ 313/DALY gained from the public perspective and US$ 37/DALY gained from the societal perspective. Even under the most conservative assumption, the intervention remained cost effective from both perspectives.

Conclusions  Annual, targeted larviciding campaigns appear to have been effective and cost‐effective medium‐term interventions to reduce the epidemiologic and economic burden of dengue in urban areas of Cambodia.
Atypical manifestations of dengue
Authors: Gulati Sameer , Maheshwari Anu
Published: August 2010

As the spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. This review compiles descriptions of atypical manifestations of dengue, such as dengue encephalitis, dengue myocarditis, dengue hepatitis and dengue cholecystitis.
Short communication: First record of Aedes albopictus in Gabon, Central Africa
Authors: Krueger Andreas , Hagen Ralf M.
Published: August 2010

The Asian tiger mosquito Aedes albopictus is an important arbovirus vector. Originating in East Asia, the species has been introduced to the Americas, the Indo‐Pacific and Australasian regions as well as Europe and Africa, mostly during the past 30 years and probably by transportation in used tires. We report Ae. albopictus for the first time from Gabon (Libreville). In addition, the yellow fever mosquito Ae. aegypti ssp. formosus and 16 other culicid species were detected throughout the city, four of which are also new records for Gabon.
Laboratory diagnosis of pulmonary tuberculosis in TB and HIV endemic settings and the contribution of real time PCR for M. tuberculosis in bronchoalveolar lavage fluid
Authors: Kibiki Gibson S. , Mulder Bert , Van Der Ven Andre J. A. M. , Sam Noel , Boeree Martin J. , Van Der Zanden Adri , Dolmans Wil M. V.
Published: August 2010

Background  Tuberculosis (TB) in Africa is increasing because of the human immunodeficiency virus (HIV) epidemic, and in HIV/AIDS patients it presents atypically. Pulmonary tuberculosis (PTB) in Africa is mainly diagnosed clinically, by chest radiograph or by sputum smear for acid fast bacilli (AFB).

Methods  We evaluated in 120 HIV‐infected patients with chest infection the diagnostic accuracy of AFB smear of sputum and bronchoalveolar lavage (BAL) fluid, sputum Mycobacterium tuberculosis (MTB) culture, real‐time PCR and MycoDot® serological test, using MTB culture of BAL fluid as gold standard. We correlated PCR cycle threshold values (CT) to the culture results. Retrospectively, we evaluated the development of active TB in patients with positive PCR but negative culture.

Results  Culture of BAL fluid identified 28 patients with PTB. Fifty‐six patients could not produce adequate sputum. Sputum AFB smear and the serological test had sensitivities of 66.7% and 0%, respectively. PCR with CT 40 was positive in 73 patients, 27 of whom were also TB culture positive (96.4% sensitivity and 52.3% specificity of PCR). PCR with CT 32 had sensitivity of 85.7% and specificity of 90.9% to diagnose PTB in BAL. No patients with positive PCR but negative culture developed active TB during 18 months follow‐up.

Conclusion  In these HIV‐infected patients, AFB smear and serology had very low sensitivities. PCR of BAL with CT value 32 had improved specificity to diagnose active PTB. A prospective follow‐up study is warranted in TB/HIV endemic settings, applying real time PCR to both sputum and BAL.
Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci
Authors: Dellicour Stephanie , Greenwood Brian
Published: August 2010

Objective  To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci.

Methods  Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review.

Results  Twenty‐nine studies satisfied the inclusion criteria. Twenty‐five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer‐membrane vaccines on overall and/or serogroup‐specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup‐specific carriage; seven of these focussed on high‐risk groups and had a short follow‐up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer‐membrane protein vaccines showed no effect on carriage.

Conclusions  A few well‐designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa.
Low specificity of the Murex fourth‐generation HIV enzyme immunoassay in Tanzanian adolescents
Authors: Everett Dean B. , Weiss Helen A. , Changalucha John , Anemona Alessandra , Chirwa Tobias , Ross David A. , Watson‐Jones Deborah , Parry John V. , Hayes Richard , Mabey David C.
Published: August 2010

Objective  To determine the specificity of the Abbott Murex HIV antigen/antibody combination enzyme immunoassay (EIA) for the diagnosis of HIV infection in Tanzania.

Methods  A cross‐sectional survey of 7333 Tanzanian adolescents and young adults was carried out. Sera testing positive by the Murex assay were further evaluated using a battery of other EIA which detect either antibody to HIV‐1 or p24 antigen, and by PCR using pol primers.

Results  Of the 674 sera testing positive by the Murex assay, only 53 (7.9%) were confirmed. The specificity of the Murex assay was 91.5%.

Conclusions  Serological tests for HIV may perform differently in different populations. New diagnostic tests should not be introduced into populations in which they have not been evaluated.
Food safety aspects of toxic element accumulation in fish from wastewater‐fed ponds in Hanoi, Vietnam
Authors: Marcussen Helle , Holm Peter E. , Ha Le Thai , Dalsgaard Anders
Published: August 2010

Objective  To evaluate the food safety of fish from production systems in Hanoi feed with domestic and industrial wastewater with respect to the potentially toxic elements such as arsenic (As), cadmium (Cd) and lead (Pb).

Methods  Common carp (Cyprinus carpio), silver carp (Hypophthalmichthys molitrix) and tilapia (Oreochromis niloticus) were sampled from wastewater‐fed ponds, and total concentrations of As, Cd and Pb were determined in skin, liver and muscle.

Results  Arsenic, Cd and Pd concentrations were generally low and for many samples below the detection limit. The highest concentrations of Cd and Pb were found in the liver of tilapia, and the highest As concentration in the skin of tilapia. Maximum concentrations in muscle tissue were 0.120, 0.079 and 0.082 mg/kg fresh weight (f.w.) for As, Cd and Pb, respectively. Consumption of fish with maximum muscle tissue concentration will result in a human intake corresponding to 6.2%, 8.7% and 2.5% of the tolerable intake of these elements set by Codex Alimentarious Commission.

Conclusion  The consumption of common carp, silver carp and tilapia produced in wastewater‐fed ponds of Hanoi seems not to constitute a food safety problem with respect to As, Cd and Pb.
Skin disease among farmers using wastewater in rice cultivation in Nam Dinh, Vietnam
Authors: Trang Do Thuy , Van Der Hoek Wim , Tuan Nguyen Dang , Cam Phung Dac , Viet Vu Huu , Luu Do Duc , Konradsen Flemming , Dalsgaard Anders
Published: August 2010

Objective  To assess the risk of skin disease among farmers occupationally exposed to wastewater.

Methods  One‐year follow‐up study with monthly assessments of wastewater exposure and skin disease in Nam Dinh, northern Vietnam, in two adjacent communes with contrasting levels of wastewater use. In each commune, 200 households were randomly selected.

Results  Of the 1103 individuals aged ≥15 years, 381 reported a skin problem at baseline or at any of the monthly visits, primarily dermatitis (eczema) and superficial fungal infections. Among the 874 subjects who were free from skin disease at baseline and who could be followed up ≥11 months, 183 developed a new skin disease (cumulative incidence 21%). Exposure to wastewater was a major risk factor for skin disease with a relative risk (RR) of 1.89 [95% confidence interval (CI) 1.39–2.57] in multivariable analysis. Other risk factors for skin disease were involvement in agriculture in general (RR = 2.59, 95% CI 1.11–6.02), flower cultivation (RR = 1.36, 95% CI 1.01–1.83), vegetable farming (RR = 1.47, 95% CI 1.04–2.08), and a history of eczema (RR = 1.47, 95% CI 1.05–2.05).

Conclusion  Exposure to wastewater is a major risk factor for skin disease. In future studies, an attempt should be made to link specific chemical or biological agents in the wastewater to specific skin diseases.
Sleeping hearts: the role of the heart in sleeping sickness (human African trypanosomiasis)
Authors: Blum Johannes A. , Burri Christian , Hatz Christoph , Kazumba Leon , Mangoni Patrick , Zellweger Michael J.
Published: August 2010

Objectives  To estimate the frequency and evolution of heart involvement in human African trypanosomiasis (HAT) using electrocardiogram (ECG) findings; to describe these findings and to assess the frequency and clinical relevance of symptoms and signs before and after treatment.

Methods  In a prospective cohort study ECG findings, signs and symptoms consistent with heart failure and cardiac laboratory parameters were studied at baseline, 2 days after the end of treatment and 3 months later.

Results  Major ECG alterations were significantly more frequent in HAT patients than in healthy controls (71%vs. 18%; P < 0.001); 31% were low voltage changes, 34% were repolarization changes. ECG signs of necrosis and conduction problems were rare. Symptoms consistent with heart failure such as exertional dyspnoea (19%vs. 1.7%; P = 0.002) or palpitations (18%vs. 5%; P = 0.28) occurred more frequently in patients than in controls. The median NT‐proBNP was significantly higher in HAT patients than in controls (85.2 vs. 28 pg/ml; P < 0.001). Troponin levels were normal. At the end of treatment repolarization changes appeared or worsened in 33.4%. Such changes improved or disappeared at follow‐up in 33.1% of the patients.

Conclusions  Cardiac involvement documented by ECG alterations is common in HAT patients, but cardiopathy rarely causes severe congestive heart failure and subsides after treatment. ECG alterations immediately after treatment and their improvement 3 months later may be the result of a treatment‐induced inflammatory reaction.
Midwifery provision and uptake of maternity care in Indonesia
Authors: Achadi Endang , Scott Susana , Pambudi Eko S. , Makowiecka Krystyna , Marshall Tom , Adisasmita Asri , Deviany Poppy E , Ronsmans Carine
Published: August 2010

Objectives  To examine the association between midwife density, other characteristics of midwifery provision and village contextual factors, and the percentage of births attended by a health professional and deliveries via caesarean section in two districts in West Java, Indonesia.

Methods  Analysis of: (i) a census of midwives; (ii) a population‐based survey of women who had delivered over a 2‐year period; (iii) a census of all caesareans in the four hospitals serving the two districts; and (iv) data from National Statistical Office.

Results  At an average density of 2.2 midwives per 10 000 population, 33% of births are with a health professional, and 1% by caesarean section. Having at least six midwives per 10 000 population was associated with a fourfold increase in caesareans [adjusted risk ratio (RR) 4.3: 95% confidence interval (CI): 3.3–5.5] and a threefold increase in the odds of having a health professional attend the delivery [adjusted odds ratio (OR) 2.88: 95% CI: 0.96–8.70]. The assigned midwife’s professional status and the duration of her service in the village were also associated with higher rates of health professionals’ attendance of delivery and caesareans. Regardless of the provision of services, women’s education and wealth were strong predictors of delivery with a health professional.

Conclusions  Promoting a stable workforce of midwives, better financial access for the poor and expanding female education are important for the achievement of the fifth Millennium Development Goal (MDG‐5).
Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub‐Saharan Africa
Authors: Rowe Alexander K. , Steketee Richard W. , Arnold Fred , Wardlaw Tessa , Basu Suprotik , Bakyaita Nathan , Lama Marcel , Winston Carla A. , Lynch Matthew , Cibulskis Richard E. , Shibuya Kenji , Ratcliffe Amy A. , Nahlen Bernard L. ,   for the Roll Back Malaria Monitoring and Evaluation Reference Group
Published: August 2010

Objective  To describe an approach for evaluating the impact of malaria control efforts on malaria‐associated mortality in sub‐Saharan Africa, where disease‐specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children.

Methods  Methods for evaluating changes in malaria‐associated mortality are examined; advantages and disadvantages are presented.

Results  All methods require a plausibility argument—i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale‐up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria‐associated morbidity (especially anaemia), and all‐cause childhood mortality. This approach reflects decreases in malaria’s direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well‐recognized limitations; however, in specific circumstances, they could produce reliable trends. Model‐based predictions can help describe changes in malaria‐specific burden and assist with program management and advocacy.

Conclusions  Despite challenges, efforts to reduce malaria‐associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all‐cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria‐specific mortality could be added.
Incidence of primary dengue virus infections in Southern Vietnamese children and reactivity against other flaviviruses
Authors: Thai Khoa T. D. , Nga Tran Thi Thanh , Van Nam Nguyen , Phuong Hoang Lan , Giao Phan Trong , Hung Le Quoc , Binh Tran Quang , Van Doornum Gerard J. J. , De Vries Peter J.
Published: August 2010

Objective To study the incidence of asymptomatic primary dengue infections among children and reactivity against other flaviviruses.

Methods A total of 216 children, who had no dengue‐specific IgG antibodies during a serosurvey in 2003 were re‐examined 23 months later to determine if seroconversion had occurred. Dengue‐specific IgG was demonstrated with enzyme‐linked immunosorbent assay (ELISA) and reactivity patterns against other flaviviruses were assessed by using immunofluorescence assay (IFA).

Results Sixty‐six children had seroconverted for dengue virus‐specific IgG; the true annual incidence of primary dengue was thus 17.3% (95% CI: 13.8–21.4). Japanese Encephalitis virus (JEV)‐specific IgG antibodies were detected by IFA among three (4.6%) samples that showed seroconversion in the dengue ELISA, because of cross‐reactivity.

Conclusion Our findings highlight the high incidence of dengue among Vietnamese children; JEV infections are rare. The true annual incidence of dengue can be estimated with a single cross‐sectional seroprevalence survey.
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

Objective  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

Objectives  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

We 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

Objective  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

Objective  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

Objectives  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

Objective  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

Objective  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

Objective  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

Objective  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

Objective  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

Objective  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

Objective  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.