Infection intensity-dependent accuracy of reagent strip for the diagnosis of Schistosoma haematobium and estimation of treatment prevalence thresholds.

BACKGROUND: Reagent strip to detect microhematuria as a proxy for Schistosoma haematobium infections has been considered an alternative to urine filtration for individual diagnosis and community-based estimates of treatment needs for preventive chemotherapy. However, the diagnostic accuracy of reagent strip needs further investigation, particularly at low infection intensity levels. METHODS: We used existing data from a study conducted in Tanzania that employed urine filtration and reagent strip testing for S. haematobium in two villages, including a baseline and six follow-up surveys after praziquantel treatment representing a wide range of infection prevalence. We developed a Bayesian model linking individual S. haematobium egg count data based on urine filtration to reagent strip binary test results available on multiple days and estimated the relation between infection intensity and sensitivity of reagent strip. Furthermore, we simulated data from 3,000 hypothetical populations with varying mean infection intensity to infer on the relation between prevalence observed by urine filtration and the interpretation of reagent strip readings. PRINCIPAL FINDINGS: Reagent strip showed excellent sensitivity even for single measurement reaching 100% at around 15 eggs of S. haematobium per 10 ml of urine when traces on reagent strip were considered positive. The corresponding specificity was 97%. When traces were considered negative, the diagnostic accuracy of the reagent strip was equivalent to urine filtration data obtained on a single day. A 10% and 50% urine filtration prevalence based on a single day sampling corresponds to 11.2% and 48.6% prevalence by reagent strip, respectively, when traces were considered negative, and 17.6% and 57.7%, respectively, when traces were considered positive. CONCLUSIONS/SIGNIFICANCE: Trace results should be included in reagent strip readings when high sensitivity is required, but excluded when high specificity is needed. The observed prevalence of reagent strip results, when traces are considered negative, is a good proxy for prevalence estimates of S. haematobium infection by urine filtration on a single day.

Policy analysis for deciding on a malaria vaccine RTS,S in Tanzania.

BACKGROUND: Traditionally, it has taken decades to introduce new interventions in low-income countries. Several factors account for these delays, one of which is the absence of a framework to facilitate comprehensive understanding of policy process to inform policy makers and stimulate the decision-making process. In the case of the proposed introduction of malaria vaccines in Tanzania, a specific framework for decision-making will speed up the administrative process and shorten the time until the vaccine is made available to the target population. METHODS: Qualitative research was used as a basis for developing the Policy Framework. Interviews were conducted with government officials, bilateral and multilateral partners and other stakeholders in Tanzania to assess malaria treatment policy changes and to draw lessons for malaria vaccine adoption. RESULTS: The decision-making process for adopting malaria interventions and new vaccines in general takes years, involving several processes: meetings and presentations of scientific data from different studies with consistent results, packaging and disseminating evidence and getting approval for use by the Ministry of Health and Social Welfare (MOHSW). It is influenced by contextual factors; Promoting factors include; epidemiological and intervention characteristics, country experiences of malaria treatment policy change, presentation and dissemination of evidence, coordination and harmonization of the process, use of international scientific evidence. Barriers factors includes; financial sustainability, competing health and other priorities, political will and bureaucratic procedures, costs related to the adoption and implementations of interventions, supply and distribution and professional compliance with anti-malarial drugs. CONCLUSION: The framework facilitates the synthesis of information in a coherent way, enabling a clearer understanding of the policy process, thereby speeding up the policy decision-making process and shortening the time for a malaria vaccine to become available.

Effectiveness of a Home-Based Counselling Strategy on Neonatal Care and Survival: A Cluster-Randomised Trial in Six Districts of Rural Southern Tanzania.

BACKGROUND: We report a cluster-randomised trial of a home-based counselling strategy, designed for large-scale implementation, in a population of 1.2 million people in rural southern Tanzania. We hypothesised that the strategy would improve neonatal survival by around 15%. METHODS AND FINDINGS: In 2010 we trained 824 female volunteers to make three home visits to women and their families during pregnancy and two visits to them in the first few days of the infant's life in 65 wards, selected randomly from all 132 wards in six districts in Mtwara and Lindi regions, constituting typical rural areas in Southern Tanzania. The remaining wards were comparison areas. Participants were not blinded to the intervention. The primary analysis was an intention-to-treat analysis comparing the neonatal mortality (day 0-27) per 1,000 live births in intervention and comparison wards based on a representative survey in 185,000 households in 2013 with a response rate of 90%. We included 24,381 and 23,307 live births between July 2010 and June 2013 and 7,823 and 7,555 live births in the last year in intervention and comparison wards, respectively. We also compared changes in neonatal mortality and newborn care practices in intervention and comparison wards using baseline census data from 2007 including 225,000 households and 22,243 births in five of the six intervention districts. Amongst the 7,823 women with a live birth in the year prior to survey in intervention wards, 59% and 41% received at least one volunteer visit during pregnancy and postpartum, respectively. Neonatal mortality reduced from 35.0 to 30.5 deaths per 1,000 live births between 2007 and 2013 in the five districts, respectively. There was no evidence of an impact of the intervention on neonatal survival (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.9-1.2, p = 0.339). Newborn care practices reported by mothers were better in intervention than in comparison wards, including immediate breastfeeding (42% of 7,287 versus 35% of 7,008, OR 1.4, CI 1.3-1.6, p < 0.001), feeding only breast milk for the first 3 d (90% of 7,557 versus 79% of 7,307, OR 2.2, 95% CI 1.8-2.7, p < 0.001), and clean hands for home delivery (92% of 1,351 versus 88% of 1,799, OR 1.5, 95% CI 1.0-2.3, p = 0.033). Facility delivery improved dramatically in both groups from 41% of 22,243 in 2007 and was 82% of 7,820 versus 75% of 7,553 (OR 1.5, 95% CI 1.2-2.0, p = 0.002) in intervention and comparison wards in 2013. Methodological limitations include our inability to rule out some degree of leakage of the intervention into the comparison areas and response bias for newborn care behaviours. CONCLUSION: Neonatal mortality remained high despite better care practices and childbirth in facilities becoming common. Public health action to improve neonatal survival in this setting should include a focus on improving the quality of facility-based childbirth care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022788.

Assessment of parental perception of malaria vaccine in Tanzania.

BACKGROUND: Clinical trials of the RTS,S malaria vaccine have completed Phase III and the vaccine is on track for registration. Before making decisions about implementation, it is essential to prepare the ground for introducing the vaccine by assessing awareness and willingness to use malaria vaccines and to provide policy makers with evidence-based information on the best strategies to engage communities to manage the introduction of malaria vaccine in Tanzania. METHODS: In November 2011, as part of a large cross-sectional study of all 23 regions of Tanzania (mainland Tanzania and Zanzibar) was conducted during Tanzanian Integrated Measles Campaign (IMC) survey. In this study, the variables of interests were awareness and willingness to use a malaria vaccine. The main outcome measure was willingness to use a malaria vaccine. Logistic regression was used to examine the influence of predictive factors. RESULTS: A representative sample of 5502 (out of 6210) women, aged 18 years or older and with children under 11 months old, was selected to participate, using random sampling probability. Awareness of the forthcoming malaria vaccine, 11.8 % of participants in mainland Tanzania responded affirmatively, compared to 3.4 % in Zanzibar (p value <0.0001). 94.5 % of all respondents were willing to vaccinate their children against malaria, with a slight difference between mainland Tanzania (94.3 %) and Zanzibar (96.8 %) (p value = 0.0167). CONCLUSIONS: Although mothers had low awareness and high willingness to use malaria vaccine, still availability of malaria vaccine RTS,S will compliment other existing malaria interventions and it will be implemented through the Immunization, Vaccines and Biologicals (IVB) programme (formerly EPI). The information generated from this study can aid policy makers in planning and setting priorities for introducing and implementing the malaria vaccine.

Setting research priorities across science, technology, and health sectors: the Tanzania experience.

BACKGROUND: Identifying research priorities is key to innovation and economic growth, since it informs decision makers on effectively targeting issues that have the greatest potential public benefit. As such, the process of setting research priorities is of pivotal importance for favouring the science, technology, and innovation (STI)-driven development of low- and middle-income countries. METHODS: We report herein on a major cross-sectoral nationwide research priority setting effort recently carried out in Tanzania by the Tanzania Commission for Science and Technology (COSTECH) in partnership with the Council on Health Research for Development (COHRED) and the NEPAD Agency. The first of its type in the country, the process brought together stakeholders from 42 sub-sectors in science, technology, and health. The cross-sectoral research priority setting process consisted of a 'training-of-trainers' workshop, a demonstration workshop, and seven priority setting workshops delivered to representatives from public and private research and development institutions, universities, non-governmental organizations, and other agencies affiliated to COSTECH. RESULTS: The workshops resulted in ranked listings of research priorities for each sub-sector, totalling approximately 800 priorities. This large number was significantly reduced by an expert panel in order to build a manageable instrument aligned to national development plans that could be used to guide research investments. CONCLUSIONS: The Tanzania experience is an instructive example of the challenges and issues to be faced in when attempting to identify research priority areas and setting an STI research agenda in low- and middle-income countries. As countries increase their investment in research, it is essential to increase investment in research management and governance as well, a key and much needed capacity for countries to make proper use of research investments.

Effect of home-based counselling on newborn care practices in southern Tanzania one year after implementation: a cluster-randomised controlled trial.

BACKGROUND: In Sub-Saharan Africa over one million newborns die annually. We developed a sustainable and scalable home-based counselling intervention for delivery by community volunteers in rural southern Tanzania to improve newborn care practices and survival. Here we report the effect on newborn care practices one year after full implementation. METHODS: All 132 wards in the 6-district study area were randomised to intervention or comparison groups. Starting in 2010, in intervention areas trained volunteers made home visits during pregnancy and after childbirth to promote recommended newborn care practices including hygiene, breastfeeding and identification and extra care for low birth weight babies. In 2011, in a representative sample of 5,240 households, we asked women who had given birth in the previous year both about counselling visits and their childbirth and newborn care practices. RESULTS: Four of 14 newborn care practices were more commonly reported in intervention than comparison areas: delaying the baby's first bath by at least six hours (81% versus 68%, OR 2.0 (95% CI 1.2-3.4)), exclusive breastfeeding in the three days after birth (83% versus 71%, OR 1.9 (95% CI 1.3-2.9)), putting nothing on the cord (87% versus 70%, OR 2.8 (95% CI 1.7-4.6)), and, for home births, tying the cord with a clean thread (69% versus 39%, OR 3.4 (95% CI 1.5-7.5)). For other behaviours there was little evidence of differences in reported practices between intervention and comparison areas including childbirth in a health facility or with a skilled attendant, thermal care practices, breastfeeding within an hour of birth and, for home births, the birth attendant having clean hands, cutting the cord with a clean blade and birth preparedness activities. CONCLUSIONS: A home-based counselling strategy using volunteers and designed for scale-up can improve newborn care behaviours in rural communities of southern Tanzania. Further research is needed to evaluate if, and at what cost, these gains will lead to improved newborn survival. TRIAL REGISTRATION: Trial Registration Number NCT01022788 (http://www.clinicaltrials.gov, 2009).

Institutional evolution of a community-based programme for malaria control through larval source management in Dar es Salaam, United Republic of Tanzania.

BACKGROUND: Community-based service delivery is vital to the effectiveness, affordability and sustainability of vector control generally, and to labour-intensive larval source management (LSM) programmes in particular. CASE DESCRIPTION: The institutional evolution of a city-level, community-based LSM programme over 14 years in urban Dar es Salaam, Tanzania, illustrates how operational research projects can contribute to public health governance and to the establishment of sustainable service delivery programmes. Implementation, management and governance of this LSM programme is framed within a nested set of spatially-defined relationships between mosquitoes, residents, government and research institutions that build upward from neighbourhood to city and national scales. DISCUSSION AND EVALUATION: The clear hierarchical structure associated with vertical, centralized management of decentralized, community-based service delivery, as well as increasingly clear differentiation of partner roles and responsibilities across several spatial scales, contributed to the evolution and subsequent growth of the programme. CONCLUSIONS: The UMCP was based on the principle of an integrated operational research project that evolved over time as the City Council gradually took more responsibility for management. The central role of Dar es Salaam's City Council in coordinating LSM implementation enabled that flexibility; the institutionalization of management and planning in local administrative structures enhanced community-mobilization and funding possibilities at national and international levels. Ultimately, the high degree of program ownership by the City Council and three municipalities, coupled with catalytic donor funding and technical support from expert overseas partners have enabled establishment of a sustainable, internally-funded programme implemented by the National Ministry of Health and Social Welfare and supported by national research and training institutes.

Child mortality patterns in rural Tanzania: an observational study on the impact of malaria control interventions.

BACKGROUND: Between 1997 and 2009, a number of key malaria control interventions were implemented in the Kilombero and Ulanga Districts in south central Tanzania to increase insecticide-treated nets (ITN) coverage and improve access to effective malaria treatment. In this study we estimated the contribution of these interventions to observed decreases in child mortality. METHODS: The local Health and Demographic Surveillance Site (HDSS) provided monthly estimates of child mortality rates (age 1 to 5 years) expressed as cases per 1000 person-years (c/1000py) between 1997 and 2009. We conducted a time series analysis of child mortality rates and explored the contribution of rainfall and household food security. We used Poisson regression with linear and segmented effects to explore the impact of malaria control interventions on mortality. RESULTS: Child mortality rates decreased by 42.5% from 14.6 c/1000py in 1997 to 8.4 c/1000py in 2009. Analyses revealed the complexity of child mortality patterns and a strong association with rainfall and food security. All malaria control interventions were associated with decreases in child mortality, accounting for the effect of rainfall and food security. CONCLUSIONS: Reaching the fourth Millenium Development Goal will require the contribution of many health interventions, as well as more general improvements in socio-environmental and nutritional conditions. Distinguishing between the effects of these multiple factors is difficult and represents a major challenge in assessing the effect of routine interventions. However, this study suggests that credible estimates can be obtained when high-quality data on the most important factors are available over a sufficiently long time period.

Health system support for childbirth care in Southern Tanzania: results from a health facility census.

BACKGROUND: Progress towards reaching Millennium Development Goals four (child health) and five (maternal health) is lagging behind, particularly in sub-Saharan Africa, despite increasing efforts to scale up high impact interventions. Increasing the proportion of birth attended by a skilled attendant is a main indicator of progress, but not much is known about the quality of childbirth care delivered by these skilled attendants. With a view to reducing maternal mortality through health systems improvement we describe the care routinely offered in childbirth at dispensaries, health centres and hospitals in five districts in rural Southern Tanzania. We use data from a health facility census assessing 159 facilities in five districts in early 2009. A structural and operational assessment was undertaken based on staff reports using a modular questionnaire assessing staffing, work load, equipment and supplies as well as interventions routinely implemented during childbirth. RESULTS: Health centres and dispensaries attended a median of eight and four deliveries every month respectively. Dispensaries had a median of 2.5 (IQR 2-3) health workers including auxiliary staff instead of the recommended four clinical officer and certified nurses. Only 28% of first-line facilities (dispensaries and health centres) reported offering active management in the third stage of labour (AMTSL). Essential childbirth care comprising eight interventions including AMTSL, infection prevention, partograph use including foetal monitoring and newborn care including early breastfeeding, thermal care at birth and prevention of ophthalmia neonatorum was offered by 5% of dispensaries, 38% of health centres and 50% of hospitals consistently. No first-line facility had provided all signal functions for emergency obstetric complications in the previous six months. CONCLUSIONS: Essential interventions for childbirth care are not routinely implemented in first-line facilities or hospitals. Dispensaries have both low staffing and low caseload which constrains the ability to provide high-quality childbirth care. Improvements in quality of care are essential so that women delivering in facility receive "skilled attendance" and adequate care for common obstetric complications such as post-partum haemorrhage.

Timeliness and completeness of vaccination and risk factors for low and late vaccine uptake in young children living in rural southern Tanzania.

BACKGROUND: We studied coverage and timeliness of vaccination and risk factors for low and delayed vaccine uptake in children aged <2 years in rural Tanzania. METHODS: We used data from a cluster survey conducted in 2004, which included 1403 children. Risk factors were analysed by log-binomial regression adjusted for the clustering. The analysis was restricted to BCG, first and third dose of Diphtheria-Tetanus-Pertussis vaccines (DTP-1 and DTP-3) and first dose of measles-containing vaccine (MCV-1). RESULTS: Coverage for BCG, DTP-1, DTP-3 and MCV-1 was 94%, 96%, 90% and 86%, respectively. Delayed vaccination (>1 month after the recommended age) occurred in 398/1205 (33%) children for BCG, 404/1189 (34%) for DTP-1, 683/990 (69%) for DTP-3 and 296/643 (46%) for MCV-1. Coverage was lower for all vaccines except DTP-1 in children living ≥5 km from a healthcare facility. Delayed uptake was associated with poverty. Low and delayed MCV-1 vaccination was associated with low maternal education. Delayed BCG vaccination was associated with ethnicity and rainy season. CONCLUSION: Despite reasonably high vaccination coverage, we observed substantial vaccination delays, particularly for DTP-3 and MCV-1. We found specific factors associated with low and/or delayed vaccine uptake. These findings can help to improve strategies to reach children who remain inadequately protected.

Clean home-delivery in rural Southern Tanzania: barriers, influencers, and facilitators.

The study explored the childbirth-related hygiene and newborn care practices in home-deliveries in Southern Tanzania and barriers to and facilitators of behaviour change. Eleven home-birth narratives and six focus group discussions were conducted with recently-delivering women; two focus group discussions were conducted with birth attendants. The use of clean cloth for delivery was reported as common in the birth narratives; however, respondents did not link its use to newborn's health. Handwashing and wearing of gloves by birth attendants varied and were not discussed in terms of being important for newborn's health, with few women giving reasons for this behaviour. The lack of handwashing and wearing of gloves was most commonly linked to the lack of water, gloves, and awareness. A common practice was the insertion of any family member's hands into the vagina of delivering woman to check labour progress before calling the birth attendant. The use of a new razor blade to cut the cord was near-universal; however, the cord was usually tied with a used thread due to the lack of knowledge and the low availability of clean thread. Applying something to the cord was near-universal and was considered essential for newborn's health. Three hygiene practices were identified as needing improvement: family members inserting a hand into the vagina of delivering woman before calling the birth attendant, the use of unclean thread, and putting substances on the cord. Little is known about families conducting internal checks of women in labour, and more research is needed before this behaviour is targeted in interventions. The use of clean thread as cord-tie appears acceptable and can be addressed, using the same channels and methods that were used for successfully encouraging the use of new razor blade.

Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02(D) malaria vaccine in infants living in a malaria-endemic region.

BACKGROUND: The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. METHODS: This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. RESULTS: From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). CONCLUSIONS: The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185.

A community-randomized evaluation of the effect of intermittent preventive treatment in infants on antimalarial drug resistance in southern Tanzania.

BACKGROUND: Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance. METHODS: Twenty-four areas were randomly assigned to receive or not receive IPTi. Blood collected during representative household surveys at baseline and 15 and 27 months after implementation was tested for SP and resistance markers. RESULTS: The frequency of SP in blood was similar in the IPTi and comparison areas at baseline and at 15 months. dhfr and dhps mutations were also similar at baseline and then increased similarly in both arms after 15 months of SP-IPTi. First-line treatment was switched from SP to artemether-lumefantrine before the final survey, when SP positivity fell among infants in comparison areas but increased in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations in IPTi areas (P = .004 and P = .18, respectively). CONCLUSIONS: IPTi did not increase drug pressure or the selection on dhfr and dhps mutants, when SP was the first-line malaria treatment. Introduction of artemether-lumefantrine was followed by an increase in dhfr mutations, consistent with weak selection attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a fitness cost of this mutation.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION: The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Acceptability--a neglected dimension of access to health care: findings from a study on childhood convulsions in rural Tanzania.

BACKGROUND: Acceptability is a poorly conceptualized dimension of access to health care. Using a study on childhood convulsion in rural Tanzania, we examined social acceptability from a user perspective. The study design is based on the premise that a match between health providers' and clients' understanding of disease is an important dimension of social acceptability, especially in trans-cultural communication, for example if childhood convulsions are not linked with malaria and local treatment practices are mostly preferred. The study was linked to health interventions with the objective of bridging the gap between local and biomedical understanding of convulsions. METHODS: The study combined classical ethnography with the cultural epidemiology approach using EMIC (Explanatory Model Interview Catalogue) tool. EMIC interviews were conducted in a 2007/08 convulsion study (n = 88) and results were compared with those of an earlier 2004/06 convulsion study (n = 135). Earlier studies on convulsion in the area were also examined to explore longer-term changes in treatment practices. RESULTS: The match between local and biomedical understanding of convulsions was already high in the 2004/06 study. Specific improvements were noted in form of (1) 46% point increase among those who reported use of mosquito nets to prevent convulsion (2) 13% point decrease among caregivers who associated convulsion with 'evil eye and sorcery', 3) 14% point increase in prompt use of health facility and 4)16% point decrease among those who did not use health facility at all. Such changes can be partly attributed to interventions which explicitly aimed at increasing the match between local and biomedical understanding of malaria. Caregivers, mostly mothers, did not seek advice on where to take an ill child. This indicates that treatment at health facility has become socially acceptable for severe febrile with convulsion. CONCLUSION: As an important dimension of access to health care 'social acceptability' seems relevant in studying illnesses that are perceived not to belong to the biomedical field, specifically in trans-cultural societies. Understanding the match between local and biomedical understanding of disease is fundamental to ensure acceptability of health care services, successful control and management of health problems. Our study noted some positive changes in community knowledge and management of convulsion episodes, changes which might be accredited to extensive health education campaigns in the study area. On the other hand it is difficult to make inference out of the findings as a result of small sample size involved. In return, it is clear that well ingrained traditional beliefs can be modified with communication campaigns, provided that this change resonates with the beneficiaries.

Neonatal deaths in rural southern Tanzania: care-seeking and causes of death.

Introduction. We report cause of death and care-seeking prior to death in neonates based on interviews with relatives using a Verbal Autopsy questionnaire. Materials and Methods. We identified neonatal deaths between 2004 and 2007 through a large household survey in 2007 in five rural districts of southern Tanzania. Results. Of the 300 reported deaths that were sampled, the Verbal Autopsy (VA) interview suggested that 11 were 28 days or older at death and 65 were stillbirths. Data was missing for 5 of the reported deaths. Of the remaining 219 confirmed neonatal deaths, the most common causes were prematurity (33%), birth asphyxia (22%) and infections (10%). Amongst the deaths, 41% (90/219) were on the first day and a further 20% (43/219) on day 2 and 3. The quantitative results matched the qualitative findings. The majority of births were at home and attended by unskilled assistants. Conclusion. Caregivers of neonates born in health facility were more likely to seek care for problems than caregivers of neonates born at home. Efforts to increase awareness of the importance of early care-seeking for a premature or sick neonate are likely to be important for improving neonatal health.

Human resources for health care delivery in Tanzania: a multifaceted problem.

BACKGROUND: Recent years have seen an unprecedented increase in funds for procurement of health commodities in developing countries. A major challenge now is the efficient delivery of commodities and services to improve population health. With this in mind, we documented staffing levels and productivity in peripheral health facilities in southern Tanzania. METHOD: A health facility survey was conducted to collect data on staff employed, their main tasks, availability on the day of the survey, reasons for absenteeism, and experience of supervisory visits from District Health Teams. In-depth interview with health workers was done to explore their perception of work load. A time and motion study of nurses in the Reproductive and Child Health (RCH) clinics documented their time use by task. RESULTS: We found that only 14% (122/854) of the recommended number of nurses and 20% (90/441) of the clinical staff had been employed at the facilities. Furthermore, 44% of clinical staff was not available on the day of the survey. Various reasons were given for this. Amongst the clinical staff, 38% were absent because of attendance to seminar sessions, 8% because of long-training, 25% were on official travel and 20% were on leave. RCH clinic nurses were present for 7 hours a day, but only worked productively for 57% of time present at facility. Almost two-third of facilities had received less than 3 visits from district health teams during the 6 months preceding the survey. CONCLUSION: This study documented inadequate staffing of health facilities, a high degree of absenteeism, low productivity of the staff who were present and inadequate supervision in peripheral Tanzanian health facilities. The implications of these findings are discussed in the context of decentralized health care in Tanzania.

The evolution of pyrimethamine resistant dhfr in Plasmodium falciparum of south-eastern Tanzania: comparing selection under SP alone vs SP+artesunate combination.

BACKGROUND: Sulphadoxine-pyrimethamine (SP) resistance is now widespread throughout east and southern Africa and artemisinin compounds in combination with synthetic drugs (ACT) are recommended as replacement treatments by the World Health Organization (WHO). As well as high cure rates, ACT has been shown to slow the development of resistance to the partner drug in areas of low to moderate transmission. This study looked for evidence of protection of the partner drug in a high transmission African context. The evaluation was part of large combination therapy pilot implementation programme in Tanzania, the Interdisciplinary Monitoring Programme for Antimalarial Combination Therapy (IMPACT-TZ) METHODS: The growth of resistant dhfr in a parasite population where SP Monotherapy was the first-line treatment was measured for four years (2002-2006), and compared with the development of resistant dhfr in a neighbouring population where SP + artesunate (SP+AS) was used as the first-line treatment during the same interval. The effect of the differing treatment regimes on the emergence of resistance was addressed in three ways. First, by looking at the rate of increase in frequency of pre-existing mutant dhfr alleles under monotherapy and combination therapy. Second, by examining whether de-novo mutant alleles emerged under either treatment. Finally, by measuring diversity at three dhfr flanking microsatellite loci upstream of the dhfr gene. RESULTS: The reduction in SP selection pressure resulting from the adoption of ACT slowed the rate of increase in the frequency of the triple mutant resistant dhfr allele. Comparing between the two populations, the higher levels of genetic diversity in sequence flanking the dhfr triple mutant allele in the population where the ACT regimen had been used indicates the reduction in SP selection pressure arising from combination therapy. CONCLUSION: The study demonstrated that, alleles containing two mutations at the dhfr have arisen at least four times independently while those containing triple mutant dhfr arose only once, and were found carrying a single unique Asian-type flanking sequence, which apparently drives the spread of pyrimethamine resistance associated dhfr alleles in east Africa. SP+AS is not recommended for use in areas where SP cure rates are less than 80% but this study reports an observed principle of combination protection from an area where pyrimethamine resistance was already high.

The case for conducting first-in-human (phase 0 and phase 1) clinical trials in low and middle income countries.

BACKGROUND: Despite the increase in the number of clinical trials in low and middle income countries (LMICs), there has been little serious discussion of whether First in Human (FIH; phase 0 and phase 1) clinical trials should be conducted in LMICs, and if so, under what conditions. Based on our own experience, studies and consultations, this paper aims to stimulate debate on our contention that for products meant primarily for conditions most prevalent in LMICs, FIH trials should preferably be done first in those countries. DISCUSSION: There are scientific and pragmatic arguments that support conducting FIH trials in LMIC. Furthermore, the changing product-development and regulatory landscape, and the likelihood of secondary benefits such as capacity building for innovation and for research ethics support our argument. These arguments take into account the critical importance of protecting human subjects of research while developing capacity to undertake FIH trials. SUMMARY: While FIH trials have historically not been conducted in LMICs, the situation in some of these countries has changed. Hence, we have argued that FIH should be conducted in LMICs for products meant primarily for conditions that are most prevalent in those contexts; provided the necessary protections for human subjects are sufficient.