Opportunities and challenges for decentralised clinical trials in sub-Saharan Africa: a qualitative study.

INTRODUCTION: Digital health has gained traction in research and development, and clinical decision support systems. The COVID-19 pandemic accelerated the adoption of decentralised clinical trials (DCTs) as a mitigation and efficiency improvement strategy. We assessed the opportunities and challenges of a digital transformation in clinical research in sub-Saharan Africa from different stakeholders' perspectives. METHODS: A qualitative study, including 40 in-depth semi structured interviews, was conducted with investigators of three leading research institutions in sub-Saharan Africa and Switzerland, contract research organisations and sponsors managing clinical trials in sub-Saharan Africa. A thematic approach was used for the analysis. RESULTS: Interviewees perceived DCTs as an opportunity for trial efficiency improvement, quality improvement and reducing the burden of people participating in clinical trials. However, to gain and maintain an optimal quality of clinical trials, a transition period is necessary to tackle contextual challenges before DCTs are being implemented. The main challenges are categorised into four themes: (1) usability and practicability of the technology; (2) paradigm shift and trial data quality; (3) ethical and regulatory hurdles and (4) contextual factors (site-specific research environment and sociocultural aspects). CONCLUSION: The transformation from a site to a patient-centric model with an increased responsibility of participants should be context adapted. The transformation requires substantial investment, training of the various stakeholders and an efficient communication. Additionally, commitment of sponsors, investigators, ethics and regulatory authorities and the buy-in of the communities are essential for this change.

Is grip strength linked to body composition and cardiovascular risk markers in primary schoolchildren? Cross-sectional data from three African countries.

OBJECTIVES: Muscular strength represents a specific component of health-related fitness. Hand grip strength (HGS) is used as an indicator for musculoskeletal fitness in children. HGS can also be used as a marker of cardiometabolic risk, but most available HGS data are derived from Western high-income countries. Therefore, this study examines whether HGS is associated with body composition and markers of cardiovascular risk in children from three sub-Saharan African countries. DESIGN: Cross-sectional study. SETTING: Public primary schools (grade 1-4) in Taabo (Côte d'Ivoire), Gqeberha (South Africa) and Ifakara (Tanzania). PARTICIPANTS: Data from 467 children from Côte d'Ivoire (210 boys, 257 girls), 864 children from South Africa (429 boys, 435 girls) and 695 children from Tanzania (334 boys, 361 girls) were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Body composition (assessed via bioelectrical impedance analysis) was the primary outcome. Cardiovascular risk markers were considered as secondary outcome. Blood pressure was measured with an oscillometric monitor, and blood markers (cholesterol, triglycerides, glycated haemoglobin) via Afinion point-of-care testing. HGS (independent variable) was assessed with a hydraulic hand dynamometer. Inferential statistics are based on mixed linear regressions and analyses of covariance. RESULTS: Across all study sites, higher HGS was associated with lower body fat, higher muscle mass and higher fat-free mass (p<0.001, 3.9%-10.0% explained variance), both in boys and girls. No consistent association was found between HGS and cardiovascular risk markers. CONCLUSIONS: HGS assessment is popular due to its simplicity, feasibility, practical utility and high reliability of measurements. This is one of the first HGS studies with children from sub-Saharan Africa. There is a great need for further studies to examine whether our findings can be replicated, to develop reference values for African children, to establish links to other health outcomes, and to explore whether HGS is associated with later development of cardiovascular risk markers. TRIAL REGISTRATION NUMBER: ISRCTN29534081.

Milestones of networking and global engagements for the Regional Network on Asian Schistosomiasis and other Helminthic Zoonoses (RNAS+).

This paper introduces the three stages of development of the Regional Network on Asian Schistosomiasis and other Helminthic Zoonoses (RNAS+), namely the preparatory stage, the strengthening stage and the expanding stage. Significant achievements have been made through the help of RNAS+, particularly on research on helminthiases. As scientists, researchers, academics work closer with control authorities, elimination of these diseases is slowly getting nearer and within reach. RNAS+, at present can boast of the following strengths: (i) strong collaboration in the regional research area with support from experts on research and control; (ii) presence of experts in various areas who can improve and promote both research and control; (iii) RNAS+ has been successful in translating research output to field application; (iv) setting up a platform that is capable of advancing the mechanisms of sharing information through its website, databases, publications and meetings; (v) RNAS+ has proved that it is capable of undertaking joint collaborative projects on operational research through multi-country, multi-disease using multi-disciplinary approach and involving different academic and research institutions in the region. Most importantly, experts who are members of RNAS+ are also linked with control programmes of the endemic member countries in the region.

Challenges and way forward.

Schistosomiasis, helminthic zoonoses and NTDs constitute a considerable majority of the diseases of poverty in the world. The RNAS+ targeted zoonoses are not only problems to human and animal health, but also cause poverty in 1 billion poor livestock keepers as well as result in 2.3 billion cases of human illness and 1.7 million human deaths a year. The gaps in research of those targeted zoonoses are urgently addressed by identifying the research priority, fulfilled by improving the multisectoral cooperation and strengthening the interventions in the control programme.

Collaborative RNAS+ research: Priorities and outcomes.

Over the past 20 years, RNAS+ has been generating research results from highly collaborative projects meant to promote and advance understanding in various aspects of schistosomiasis. Epidemiological studies in endemic countries like the Philippines, the People's Republic of China (PR China), the Lao People's Democratic Republic (Lao PDR) and Cambodia clarified the role of reservoir hosts in transmission and the use of spatio-temporal methods such as remote sensing and geographical information systems (GIS) in surveillance of schistosomiasis. Morbidity studies proposed factors that might influence development of fibrosis, anaemia and malnutrition in schistosomiasis. Immune responses in schistosomiasis continue to be an interesting focus in research to explain possible development of resistance with age. Results of evaluation of candidate vaccine molecules are also presented. New diagnostics are continually being developed in response to the call for more sensitive and field applicable techniques that will be used for surveillance in areas nearing elimination of the disease. Several studies presented here show the insufficiency of mass drug administration (MDA) with praziquantel in eliminating the disease. Emphasis is given to an integrated control approach that can be accomplished through intensive and extensive intersectoral collaboration.

Needs and coordination mechanism for capacity building by the RNAS.

For the Regional Network on Asian Schistosomiasis and Other Helminth Zoonosis (RNAS+), capacity building with emphasis on modern technology with correspondence to traditional techniques was found to be a priority. This article summarized the actual needs of capacity building among RNAS+ member countries and the working mechanism of capacity building during the last 20 years. The needs with respect to the RNAS+ target diseases are highly correlated with the research priorities, since most problems with regard to the performance of the national disease control programme in the member countries are connected with inadequate capacity in relation to implementation of innovative research, epidemiological investigations, laboratory performance; and sociological investigations. The capacity building arranged through RNAS+ platform includes short training courses, individual training in member institutions, e.g., supervision of Ph.D./Masters students; postdoctoral training; and internship training in institutions of southeast Asia as well as in famous institutions of Europe and the United States. In the future, capacity building will focus on platform design and technical standardization aiming at fostering research capacity in the future. Moreover, new training projects, such as massive online courses (MOOC) will be explored under RNAS+ platform.

From country control programmes to translational research.

From the time it was conceptualized in 1998 to the present, RNAS+ has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme. The need for surveillance in areas where the prevalence has been brought down to very low levels necessitated development of spatio-temporal tools and ecological models based on geographical information systems (GIS) to produce risk and distribution maps for monitoring and evaluation of programme success. New knowledge and experiences in management of the diseases contribute to the formulation of new schemes in management and treatment. Ways of drawing attention to the disease, such as determining disability weights for use in computation of burden of disease, updating epidemiological profile and unravelling new aspects of the disease provide bases for modifying the operation of control programmes as we move forward. Programme evaluation based on reports of actual implementation of activities brought to the fore problems related to the distribution of chemotherapy as well as social, cultural and behavioural aspects of endemic communities. Importantly, this highlighted the necessity of adapting control activities to specific situations of the endemic areas. New models evolving from reviews of this kind and success stories, such us the elimination of lymphatic filariasis (LF) in PR China and Cambodia are presented.

Multi-disciplinary integration of networking through the RNAS+: Research on other target diseases.

In 2005, the network decided to increase its number of target diseases to include other helminthic zoonoses such as fascioliasis, clonorchiasis, opisthorchiasis, paragonimiasis and cysticercosis and in the process expanding membership to include South Korea, Vietnam, Thailand and Japan. NTDs were eventually included as awareness is heightened on these diseases affecting poor and developing countries. Researches on clonorchiasis and opisthorchiasis unravel the mechanism by which these diseases eventually predispose to cholangiocarcinoma. The liver cancer associated with these liver fluke infections necessitate the need to clarify the global burden of disease of these infections. The magnitude of these liver fluke diseases in endemic countries like China, Vietnam, Laos, Cambodia and Thailand is described. Success in elimination of lymphatic filariasis in PR China and Cambodia is highlighted to show how intensified multisectoral collaboration and strong political become strong ingredients in elimination of parasitic diseases like LF. New advances are presented that clarify species and strain differences in Fasciola spp., Paragonimus spp., Taenia spp. and Echinococcocus spp. Conventional diagnostic techniques are compared with new serologic techniques that are being developed. New control strategies such as the Lawa model are presented.

A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth: a study protocol.

INTRODUCTION: Preterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period. METHODS AND ANALYSIS: Four hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case-control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery. ETHICS AND DISSEMINATION: This research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15-062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33-15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT02797327; Pre-results.

Persistent Hotspots in Schistosomiasis Consortium for Operational Research and Evaluation Studies for Gaining and Sustaining Control of Schistosomiasis after Four Years of Mass Drug Administration of Praziquantel.

Control of schistosomiasis presently relies largely on preventive chemotherapy with praziquantel through mass drug administration (MDA) programs. The Schistosomiasis Consortium for Operational Research and Evaluation has concluded five studies in four countries (Côte d'Ivoire, Kenya, Mozambique, and Tanzania) to evaluate alternative approaches to MDA. Studies involved four intervention years, with final evaluation in the fifth year. Mass drug administration given annually or twice over 4 years reduced average prevalence and intensity of schistosome infections, but not all villages that were treated in the same way responded similarly. There are multiple ways by which responsiveness to MDA, or the lack thereof, could be measured. In the analyses presented here, we defined persistent hotspots (PHS) as villages that achieved less than 35% reduction in prevalence and/or less than 50% reduction in infection intensity after 4 years of either school-based or community-wide MDA, either annually or twice in 4 years. By this definition, at least 30% of villages in each of the five studies were PHSs. We found no consistent relationship between PHSs and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. New research is warranted to identify PHSs after just one or a few rounds of MDA, and new adaptive strategies need to be advanced and validated for turning PHSs into responder villages.

[Prevalence and polyparasitism of intestinal protozoa and spatial distribution of Entamoeba histolytica, E. dispar and Giardia intestinalis from pupils in the rural zone of Man in Côte d'Ivoire]. / Prévalences et polyparasitisme des protozoaires intestinaux et répartition spatiale d'Entamoeba histolytica/Entamoeba dispar et Giardia intestinalis chez des élèves en zone rurale de la région de Man en Côte-d'Ivoire.

Diseases caused by environmental contamination by micro-organisms, including intestinal helminths and protozoa, are prevalent in developing countries. According to some authors, their strong expansion in some zones of these countries is due primarily to favourable climatic conditions, combined with inadequate hygiene measures and cleaning and the generally low socio-economic level. Progress in disease control has resulted from new studies that improve our understanding of the epidemiology of helminthiases and from the availability of simple tools that are inexpensive and effective against these diseases (chemotherapy with albendazole and mebendazole). On the other hand, surprisingly few such studies have looked at intestinal protozoa, although the WHO reports that approximately 480 million individuals throughout the world are infested by amoebiasis caused by the protozoon Entamoeba histolytica and that 40,000-110,000 people die from it each year. Giardiasis, a cosmopolitan parasitosis, is due to another intestinal protozoon called Giardia intestinalis. To help develop a database on these parasites, we conducted a cross-sectional epidemiological survey in the Man region in western Côte d'Ivoire. Its objectives were to determine the prevalence of intestinal protozoa, to evaluate polyparasitism and to assess the spatial distribution of the pathogenic protozoal species, E. histolytica and G. intestinalis. Overall, 4466 stools samples taken from pupils aged 6 to 16 years of age at 57 different schools were analyzed under an optical microscope by the formol-ether stool concentration method, after preservation in sodium acetate-acetic acid-formalin (SAF). The most common protozoa species in this area were Endolimax nanus (83.8%) and E. coli (74.7%). The regional prevalence of G. intestinalis was 17.5% and of E. histolytica/E. dispar 11.3%. Both species were found in each of the 57 schools. The prevalence of E. histolytica/E. dispar exceeded 15% in six schools, and its spatial distribution was highly disparate. On the other hand, three large areas with substantial G. intestinalis transmission were identified. Polyparasitism of intestinal protozoa is very frequent in these areas; 80.2% of pupils carried at least 2 species. This work confirms the presence and breadth of protozoa species in the Man region. Understanding the spatial distribution of the principal areas where pathogenic protozoa species are transmitted may help to develop programmes for disease control that combine chemotherapy and preventive measures.

Pregnancy-related mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Women continue to die in unacceptably large numbers around the world as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of the problem is a lack of accurate, population-based information characterising the issues and informing solutions. Population surveillance sites, such as those operated within the INDEPTH Network, have the potential to contribute to bridging the information gaps. OBJECTIVE: To describe patterns of pregnancy-related mortality at INDEPTH Network Health and Demographic Surveillance System sites in sub-Saharan Africa and southeast Asia in terms of maternal mortality ratio (MMR) and cause-specific mortality rates. DESIGN: Data on individual deaths among women of reproductive age (WRA) (15-49) resident in INDEPTH sites were collated into a standardised database using the INDEPTH 2013 population standard, the WHO 2012 verbal autopsy (VA) standard, and the InterVA model for assigning cause of death. RESULTS: These analyses are based on reports from 14 INDEPTH sites, covering 14,198 deaths among WRA over 2,595,605 person-years observed. MMRs varied between 128 and 461 per 100,000 live births, while maternal mortality rates ranged from 0.11 to 0.74 per 1,000 person-years. Detailed rates per cause are tabulated, including analyses of direct maternal, indirect maternal, and incidental pregnancy-related deaths across the 14 sites. CONCLUSIONS: As expected, these findings confirmed unacceptably high continuing levels of maternal mortality. However, they also demonstrate the effectiveness of INDEPTH sites and of the VA methods applied to arrive at measurements of maternal mortality that are essential for planning effective solutions and monitoring programmatic impacts.

Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

Mortality from external causes in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System Sites.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs.

Cause-specific childhood mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Childhood mortality, particularly in the first 5 years of life, is a major global concern and the target of Millennium Development Goal 4. Although the majority of childhood deaths occur in Africa and Asia, these are also the regions where such deaths are least likely to be registered. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To present a description of cause-specific mortality rates and fractions over the first 15 years of life as documented by INDEPTH Network sites in sub-Saharan Africa and south-east Asia. DESIGN: All childhood deaths at INDEPTH sites are routinely registered and followed up with verbal autopsy (VA) interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provided person-time denominators for mortality rates. Cause-specific mortality rates and cause-specific mortality fractions are presented according to WHO 2012 VA cause groups for neonatal, infant, 1-4 year and 5-14 year age groups. RESULTS: A total of 28,751 childhood deaths were documented during 4,387,824 person-years over 18 sites. Infant mortality ranged from 11 to 78 per 1,000 live births, with under-5 mortality from 15 to 152 per 1,000 live births. Sites in Vietnam and Kenya accounted for the lowest and highest mortality rates reported. CONCLUSIONS: Many children continue to die from relatively preventable causes, particularly in areas with high rates of malaria and HIV/AIDS. Neonatal mortality persists at relatively high, and perhaps sometimes under-documented, rates. External causes of death are a significant childhood problem in some settings.

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.

HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

Therapeutic effect of artemether and artesunate in mice infected with Schistosoma mansoni / 中国血吸虫病防治杂志

Objective To explore the therapeutic effect of artemether and artesunate on adult Schistosoma mansoni in experimental mice.Methods The mice were administered intragastrically with artemether or artesunate 46 days after being infected with cercariae of S.mansoni subcutaneously. On Day 1,a dose of 400, 300, 200 mg/kg of artemether or artesunate was administered to the mice. From Day 2 to Day 7, a half above dose was administered. On Day 7, the single-dose groups were administered with artemether or artesunate at the dose of 1600, 1200, 800 mg/kg, meanwhile, an infected group of mice was served as control, untreated. Results With 7-day therapy of artemether at the dosage of 1600, 1200, 800 mg/kg, the worm reduction rates were 53%, 49% and 53%, respectively, and female worm reduction rates were from 78%-82%, compared with the control group.The therapeutic effects of artemether on single-dose groups were similar. The worm reduction rates, with 7-day therapy of artemether at the dosage of 1600, 1200, 800 mg/kg , were 16%,37% and 49%, respectively, compared with the control group. Conclusion The efficacy of therapy with artemether and artesunate on S.mansoni infection mice were relatively well. Concerning the therapeutic effect and toxicity, artemether is slightly better than artesunate.