Effects of the COVID-19 pandemic on general health and malaria control in Ghana: a qualitative study with mothers and health care professionals.

BACKGROUND: COVID-19 has severely impacted health systems and the management of non-COVID-19 diseases, including malaria, globally. The pandemic has hit sub-Saharan Africa less than expected; even considering large underreporting, the direct COVID-19 burden was minor compared to the Global North. However, the indirect effects of the pandemic, e.g. on socio-economic inequality and health care systems, may have been more disruptive. Following a quantitative analysis from northern Ghana, which showed significant reductions in overall outpatient department visits and malaria cases during the first year of COVID-19, this qualitative study aims to provide further explanations to those quantitative findings. METHODS: In the Northern Region of Ghana, 72 participants, consisting of 18 health care professionals (HCPs) and 54 mothers of children under the age of five, were recruited in urban and rural districts. Data were collected using focus group discussions with mothers and through key informant interviews with HCPs. RESULTS: Three main themes occurred. The first theme-general effects of the pandemic-includes impacts on finances, food security, health service provision as well as education and hygiene. Many women lost their jobs, which increased their dependance on males, children had to drop out of school, and families had to cope with food shortages and were considering migration. HCPs had problems reaching the communities, suffered stigmatisation and were often barely protected against the virus. The second theme-effects on health-seeking-includes fear of infection, lack of COVID-19 testing capacities, and reduced access to clinics and treatment. The third theme-effects on malaria-includes disruptions of malaria preventive measures. Clinical discrimination between malaria and COVID-19 symptoms was difficult and HCPs observed increases in severe malaria cases in health facilities due to late reporting. CONCLUSION: The COVID-19 pandemic has had large collateral impacts on mothers, children and HCPs. In addition to overall negative effects on families and communities, access to and quality of health services was severely impaired, including serious implications on malaria. This crisis has highlighted weaknesses of health care systems globally, including the malaria situation; a holistic analysis of the direct and indirect effects of this pandemic and an adapted strengthening of health care systems is essential to be prepared for the future.

Predicting the risk of malaria re-introduction in countries certified malaria-free: a systematic review.

BACKGROUND: Predicting the risk of malaria in countries certified malaria-free is crucial for the prevention of re-introduction. This review aimed to identify and describe existing prediction models for malaria re-introduction risk in eliminated settings. METHODS: A systematic literature search following the PRISMA guidelines was carried out. Studies that developed or validated a malaria risk prediction model in eliminated settings were included. At least two authors independently extracted data using a pre-defined checklist developed by experts in the field. The risk of bias was assessed using both the prediction model risk of bias assessment tool (PROBAST) and the adapted Newcastle-Ottawa Scale (aNOS). RESULTS: A total 10,075 references were screened and 10 articles describing 11 malaria re-introduction risk prediction models in 6 countries certified malaria free. Three-fifths of the included prediction models were developed for the European region. Identified parameters predicting malaria re-introduction risk included environmental and meteorological, vectorial, population migration, and surveillance and response related factors. Substantial heterogeneity in predictors was observed among the models. All studies were rated at a high risk of bias by PROBAST, mostly because of a lack of internal and external validation of the models. Some studies were rated at a low risk of bias by the aNOS scale. CONCLUSIONS: Malaria re-introduction risk remains substantial in many countries that have eliminated malaria. Multiple factors were identified which could predict malaria risk in eliminated settings. Although the population movement is well acknowledged as a risk factor associated with the malaria re-introduction risk in eliminated settings, it is not frequently incorporated in the risk prediction models. This review indicated that the proposed models were generally poorly validated. Therefore, future emphasis should be first placed on the validation of existing models.

Community engagement among forest goers in a malaria prophylaxis trial: implementation challenges and implications.

BACKGROUND: Malaria transmission in Southeast Asia is increasingly confined to forests, where marginalized groups are exposed primarily through their work. Anti-malarial chemoprophylaxis may help to protect these people. This article examines the effectiveness and practical challenges of engaging forest-goers to participate in a randomized controlled clinical trial of anti-malarial chemoprophylaxis with artemether-lumefantrine (AL) versus a control (multivitamin, MV) for malaria in northeast Cambodia. METHODS: The impact of engagement in terms of uptake was assessed as the proportion of people who participated during each stage of the trial: enrolment, compliance with trial procedures, and drug intake. During the trial, staff recorded the details of engagement meetings, including the views and opinions of participants and community representatives, the decision-making processes, and the challenges addressed during implementation. RESULTS: In total, 1613 participants were assessed for eligibility and 1480 (92%) joined the trial, 1242 (84%) completed the trial and received prophylaxis (AL: 82% vs MV: 86%, p = 0.08); 157 (11%) were lost to follow-up (AL: 11% vs MV: 11%, p = 0.79); and 73 (5%) discontinued the drug (AL-7% vs MV-3%, p = 0.005). The AL arm was associated with discontinuation of the study drug (AL: 48/738, 7% vs 25/742, 3%; p = 0.01). Females (31/345, 9%) were more likely (42/1135, 4%) to discontinue taking drugs at some point in the trial (p = 0.005). Those (45/644, 7%) who had no previous history of malaria infection were more likely to discontinue the study drug than those (28/836, 3%) who had a history of malaria (p = 0.02). Engagement with the trial population was demanding because many types of forest work are illegal; and the involvement of an engagement team consisting of representatives from the local administration, health authorities, community leaders and community health workers played a significant role in building trust. Responsiveness to the needs and concerns of the community promoted acceptability and increased confidence in taking prophylaxis among participants. Recruitment of forest-goer volunteers to peer-supervise drug administration resulted in high compliance with drug intake. The development of locally-appropriate tools and messaging for the different linguistic and low-literacy groups was useful to ensure participants understood and adhered to the trial procedures. It was important to consider forest-goers` habits and social characteristics when planning the various trial activities. CONCLUSIONS: The comprehensive, participatory engagement strategy mobilized a wide range of stakeholders including study participants, helped build trust, and overcame potential ethical and practical challenges. This locally-adapted approach was highly effective as evidenced by high levels of trial enrolment, compliance with trial procedures and drug intake.

Barriers to seeking health care among returning travellers with malaria: A systematic review.

OBJECTIVE: To identify barriers to seeking health care among returning travellers with malaria with the aim of developing targeted interventions that improve early health care-seeking behaviour, diagnosis and treatment. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review of published medical literature, selecting studies that investigated and reported barriers to seeking health care among returning travellers and migrants with malaria. In total, 633 articles were screened, of which four studies met the inclusion criteria after a full-text review. RESULTS: The four studies reported barriers to seeking healthcare among returning travellers in China, the United States, Thailand and the Dominican Republic. Three studies had an observational design. The identified barriers were summarised based on the appraisal delay, illness delay and utilisation delay stages. During appraisal delays, low awareness of malaria was the most significant factor. Once the patient assessed that he or she was ill, belonging to a specific minority ethnicity, being infected with P. vivax and receiving a low level of social support were predictors of delayed health care-seeking. Finally, the most significant factor associated with utilisation delays was the monetary cost. CONCLUSION: The health care-seeking behaviour of returning travellers with malaria should be further investigated and improved. Addressing the identified barriers and gaps in health care-seeking behaviour among returning travellers with malaria, particularly among groups at high risk of travel-associated infections, is important to prevent severe disease and deaths as well as secondary transmission and epidemics.

Impact of the COVID-19 pandemic on malaria cases in health facilities in northern Ghana: a retrospective analysis of routine surveillance data.

BACKGROUND: The COVID-19 pandemic and its collateral damage severely impact health systems globally and risk to worsen the malaria situation in endemic countries. Malaria is a leading cause of morbidity and mortality in Ghana. This study aims to describe the potential effects of the COVID-19 pandemic on malaria cases observed in health facilities in the Northern Region of Ghana. METHODS: Monthly routine data from the District Health Information Management System II (DHIMS2) of the Northern Region of Ghana were analysed. Overall outpatient department visits (OPD) and malaria case rates from the years 2015-2019 were compared to the corresponding data of the year 2020. RESULTS: Compared to the corresponding periods of the years 2015-2019, overall visits and malaria cases in paediatric and adult OPDs in northern Ghana decreased in March and April 2020, when major movement and social restrictions were implemented in response to the pandemic. Cases slightly rebounded afterwards in 2020, but stayed below the average of the previous years. Malaria data from inpatient departments showed a similar but more pronounced trend when compared to OPDs. In pregnant women, however, malaria cases in OPDs increased after the first COVID-19 wave. CONCLUSIONS: The findings from this study show that the COVID-19 pandemic affects the malaria burden in health facilities of northern Ghana, with declines in inpatient and outpatient rates except for pregnant women. They may have experienced reduced access to insecticide-treated nets and intermittent preventive malaria treatment in pregnancy, resulting in subsequent higher malaria morbidity. Further data, particularly from community-based studies and ideally complemented by qualitative research, are needed to fully determine the impact of the pandemic on the malaria situation in Africa.

Implementation and challenges to preventing the re-establishment of malaria in China in the COVID-19 era.

BACKGROUND: The rapid emergence and global spread of COVID-19 have caused substantial global disruptions that have impacted malaria programs worldwide. Innovative strategies to enable countries aiming to eliminate malaria as well as those that are already certified as malaria-free, are needed to address malaria importation in the context of the COVID-19 pandemic. China was certified as malaria-free in 2021 and now aims to prevent the malaria re-establishment. Nonpharmaceutical interventions such as entry screening, quarantining, and health education for individuals returning from international travel during the COVID-19 pandemic present both opportunities and challenges to the management of imported malaria. This study aimed to describe and analyze the operational challenges associated with an integrated surveillance and case management program in which malaria re-establishment prevention measures were incorporated into the COVID-19 program in China. METHODS: After the integration of malaria re-establishment prevention activities into the COVID-19 program for 10 months in Jiangsu Province, China, a focus-group discussion of public health workers working on preventing malaria re-establishment and controlling COVID-19 was held in June 2021, aiming to explore the operational challenges and lessons learned from the integrated approach. RESULTS: From 01 August 2020 to 31 May 2021, 8,947 overseas travelers with Yangzhou as the final destination underwent 14-day managed quarantine and 14-day home isolation. Of these travelers, 5,562 were from malaria-endemic regions. A total of 26,026 education booklets and materials were distributed to expand malaria-related knowledge. Twenty-two patients with unknown fever were screened for malaria with rapid diagnostic tests, and one patient was confirmed to have imported malaria. The challenges associated with the implementation of the integrated malaria surveillance and case management program include neglect of malaria due to COVID-19, lack of a standard operating procedure for malaria screening, mobility of public health providers, and difficulties in respecting the timeline of the "1-3-7" surveillance strategy. CONCLUSIONS: China's experience highlights the feasibility of integrated case surveillance and management of existing infectious diseases and new emerging infections. It also demonstrates the importance of a sound public health infrastructure with adequate, trained field staff for screening, testing, contact tracing, and providing health education, all of which are crucial for the success of both malaria re-establishment prevention program and the effective control of COVID-19.

[How Often is Rare Really Rare? A Survey on the Frequency of Rare Diseases at a University Hospital]. / Wie häufig ist selten wirklich? Eine Erhebung zur Häufigkeit Seltener Erkrankungen an einem Universitätsklinikum.

AIM OF STUDY: The prevalence of rare diseases in hospitals and in university hospitals is unknown. As the ICD-10 coding system does not adequately represent rare diagnoses, the prevalence of rare diseases cannot be estimated based on ICD-10 coded discharge diagnoses. The current hospital reimbursement system does not seem to be designed to capture performance-related higher expenditures in the treatment of rare diseases. The aim of this study was to help estimate the frequency of rare diseases among inpatients treated at a university hospital where documentation of rare diseases is obligatory by analyzing the case load of such diseases for a given year. METHOD: Since 2017, rare diseases have been coded for all inpatients treated at the University Hospital Dresden. This coding is based on the Orpha identification number, which was implemented in the hospital information system ORBIS for this purpose. Result For illustrative purposes, cases in 2019 were evaluated. During this period, 19% of all 70 937 inpatients seen at the University Hospital Dresden were coded as having a rare disease. CONCLUSION: For the first time, a prospective and complete documentation of rare diseases was implemented at a German university hospital. The prevalence of rare diseases of 6 to 8% as defined by the European Union was exceeded several fold. Probably it underestimates the actual prevalence considerably, since the quality of the coding correlates on user compliance. Nevertheless, the results of this survey underline the special role of patients with rare diseases in the medical care at university hospitals.

Public health-relevant consequences of the COVID-19 pandemic on malaria in sub-Saharan Africa: a scoping review.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria-endemic countries, particularly in sub-Saharan Africa (SSA). This scoping review aims to summarize information on public health-relevant effects of the COVID-19 pandemic on the malaria situation in SSA. METHODS: Review of publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from 1 December, 2019 to 9 June, 2021. A structured search was conducted on different databases using predefined eligibility criteria for the selection of articles. RESULTS: A total of 51 papers have been included in the analysis. Modelling papers have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic. Many papers provided potential explanations for expected COVID-19 effects on the malaria burden; these ranged from relevant diagnostical and clinical aspects to reduced access to health care services, impaired availability of curative and preventive commodities and medications, and effects on malaria prevention campaigns. Compared to previous years, fewer country reports provided data on the actual number of malaria cases and deaths in 2020, with mixed results. While highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020. CONCLUSIONS: The findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on malaria in SSA. There is the need to further investigate the public health consequences of the COVID-19 pandemic on the malaria burden. Protocol registered on Open Science Framework: https://doi.org/10.17605/OSF.IO/STQ9D.

Risk factors for antibiotic resistance development in healthcare settings in China: a systematic review.

Antibiotic resistance (ABR) threatens the effectiveness of infectious disease treatments and contributes to increasing global morbidity and mortality. In this study, we systematically reviewed the identified risk factors for ABR among people in the healthcare system of mainland China. Five databases were systematically searched to identify relevant articles published in either English and Chinese between 1 January 2003 and 30 June 2019. A total of 176 facility-based references were reviewed for this study, ranging across 31 provinces in mainland China and reporting information from over 50 000 patients. Four major ABR risk factor domains were identified: (1) sociodemographic factors (includes migrant status, low income and urban residence), (2) patient clinical information (includes disease status and certain laboratory results), (3) admission to healthcare settings (includes length of hospitalisation and performance of invasive procedures) and (4) drug exposure (includes current or prior antibiotic therapy). ABR constitutes an ongoing major public health challenge in China. The healthcare sector-associated risk factors was the most important aspect identified in this review and need to be addressed. Primary health care system and ABR surveillance networks need to be further strengthened to prevent and control the communicable diseases, over-prescription and overuse of antibiotics.

Challenges in the last mile of the global guinea worm eradication program.

OBJECTIVE: The objective of this study was to identify the existing challenges in the last mile of the global Guinea Worm Eradication Program. METHODS: Systematic Review of articles published from 1 January 2000 until 31 December 2019. Papers listed in Cochrane Library, Google Scholar, ProQuest PubMed and Web of Science databases were searched and reviewed. RESULTS: Twenty-five articles met inclusion criteria of the study and were selected for analysis. Hence, relevant data were extracted, grouped and descriptively analysed. Results revealed 10 main challenges complicating the last mile of global guinea worm eradication: unusual mode of transmission; rising animal guinea worm infection; suboptimal surveillance; insecurity; inaccessibility; inadequate safe water points; migration; poor case containment measures, ecological changes; and new geographic foci of the disease. CONCLUSION: This systematic review shows that most of the current challenges in guinea worm eradication have been present since the start of the campaign. However, the recent change in epidemiological patterns and nature of dracunculiasis in the last remaining endemic countries illustrates a new twist. Considering the complex nature of the current challenges, there seems to be a need for a more coordinated and multidisciplinary approach of dracunculiasis prevention and control measures. These new strategies would help to make history by eradicating dracunculiasis as the first ever parasitic disease.

OBJECTIF: L'objectif de cette étude était d'identifier les défis existants sur le dernier kilomètre du programme mondial d'éradication de la dracunculose. MÉTHODE: Revue systématique des articles publiés du 1er janvier 2000 au 31 décembre 2019. Les articles répertoriés dans les bases de données Cochrane Library, Google Scholar, ProQuest PubMed et Web of Science ont été recherchés et examinés. RÉSULTATS: Vingt-cinq articles répondaient aux critères d'inclusion de l'étude et ont été sélectionnés pour l'analyse. Par conséquent, les données pertinentes ont été extraites, regroupées et analysées de manière descriptive. Les résultats ont révélé 10 principaux défis compliquant le dernier kilomètre de l'éradication mondiale du ver de Guinée: mode de transmission inhabituel, infection animale croissante du ver de Guinée, surveillance sous-optimale, insécurité, inaccessibilité; points d'eau salubres inadéquats, migration, mauvaises mesures de confinement des cas, changements écologiques et de nouveaux foyers géographiques de la maladie. CONCLUSION: Cette revue systématique montre que la plupart des défis actuels de l'éradication du ver de Guinée ont été présents depuis le début de la campagne. Cependant, le changement récent des profils épidémiologiques et de la nature de la dracunculose dans les derniers pays d'endémie restants illustre une nouvelle tournure. Compte tenu de la nature complexe des défis actuels, il semble nécessaire d'adopter une approche plus coordonnée et multidisciplinaire des mesures de prévention et de lutte contre la dracunculose. Ces nouvelles stratégies contribueraient à faire l'histoire en permettant l'éradication de la dracunculose en tant que toute première maladie parasitaire.

Public-private knowledge transfer and access to medicines: a systematic review and qualitative study of perceptions and roles of scientists involved in HPV vaccine research.

BACKGROUND: Public research organizations and their interactions with industry partners play a crucial role for public health and access to medicines. The development and commercialization of the Human Papillomavirus (HPV) vaccines illustrate how licensing practices of public research organizations can contribute to high prices of the resulting product and affect accessibility to vulnerable populations. Efforts by the international community to improve access to medicines have recognised this issue and promote the public health-sensitive management of research conducted by public research organizations. This paper explores: how medical knowledge is exchanged between public and private actors; what role inventor scientists play in this process; and how they view the implementation of public health-sensitive knowledge exchange strategies. METHODS: We conducted a systematic qualitative literature review on medical knowledge exchange and qualitative interviews with a purposive sample of public sector scientists working on HPV vaccines. We explored the strategies by which knowledge is exchanged across institutional boundaries, how these strategies are negotiated, and the views of scientists regarding public health-sensitive knowledge exchange. RESULTS: We included 13 studies in the systematic review and conducted seven semi-structured interviews with high-ranking scientists. The main avenues of public-private medical knowledge exchange were publications, formal transfer of patented knowledge, problem-specific exchanges such as service agreements, informal exchanges and collaborative research. Scientists played a crucial role in these processes but appeared to be sceptical of public health-sensitive knowledge exchange strategies, as these were believed to deter corporate interest in the development of new medicines and thus risk the translation of the scientists' research. CONCLUSION: Medical scientists at public research institutions play a key role in the exchange of knowledge they generate and are concerned about the accessibility of medicines resulting from their research. Their scepticism towards implementing public health-sensitive knowledge management strategies appears to be based on a biased understanding of the costs and risks involved in drug development and a perceived lack of alternatives to private engagement. Scientists could be encouraged to exchange knowledge in a public health-sensitive manner through not-for-profit drug development mechanisms, education on industry engagement, and stronger institutional and legal backing.

The lichen symbiosis re-viewed through the genomes of Cladonia grayi and its algal partner Asterochloris glomerata.

BACKGROUND: Lichens, encompassing 20,000 known species, are symbioses between specialized fungi (mycobionts), mostly ascomycetes, and unicellular green algae or cyanobacteria (photobionts). Here we describe the first parallel genomic analysis of the mycobiont Cladonia grayi and of its green algal photobiont Asterochloris glomerata. We focus on genes/predicted proteins of potential symbiotic significance, sought by surveying proteins differentially activated during early stages of mycobiont and photobiont interaction in coculture, expanded or contracted protein families, and proteins with differential rates of evolution. RESULTS: A) In coculture, the fungus upregulated small secreted proteins, membrane transport proteins, signal transduction components, extracellular hydrolases and, notably, a ribitol transporter and an ammonium transporter, and the alga activated DNA metabolism, signal transduction, and expression of flagellar components. B) Expanded fungal protein families include heterokaryon incompatibility proteins, polyketide synthases, and a unique set of G-protein α subunit paralogs. Expanded algal protein families include carbohydrate active enzymes and a specific subclass of cytoplasmic carbonic anhydrases. The alga also appears to have acquired by horizontal gene transfer from prokaryotes novel archaeal ATPases and Desiccation-Related Proteins. Expanded in both symbionts are signal transduction components, ankyrin domain proteins and transcription factors involved in chromatin remodeling and stress responses. The fungal transportome is contracted, as are algal nitrate assimilation genes. C) In the mycobiont, slow-evolving proteins were enriched for components involved in protein translation, translocation and sorting. CONCLUSIONS: The surveyed genes affect stress resistance, signaling, genome reprogramming, nutritional and structural interactions. The alga carries many genes likely transferred horizontally through viruses, yet we found no evidence of inter-symbiont gene transfer. The presence in the photobiont of meiosis-specific genes supports the notion that sexual reproduction occurs in Asterochloris while they are free-living, a phenomenon with implications for the adaptability of lichens and the persistent autonomy of the symbionts. The diversity of the genes affecting the symbiosis suggests that lichens evolved by accretion of many scattered regulatory and structural changes rather than through introduction of a few key innovations. This predicts that paths to lichenization were variable in different phyla, which is consistent with the emerging consensus that ascolichens could have had a few independent origins.

Knowledge, attitudes, and practices regarding malaria control among the slash and burn cultivators in Rangamati Hill tracts of Bangladesh.

BACKGROUND: Slash and burn cultivators are a significant risk group for malaria in South-East Asia. As envisaged in the National Strategic Plan for Malaria Elimination, Bangladesh aims to achieve zero indigenous malaria transmission by 2030. For the national plan to move from malaria control to malaria elimination, targeting the population of slash and burn cultivators is of overriding importance. METHODS: The study used an explorative mixed method design to investigate the knowledge, attitudes, and practices (KAP) regarding malaria prevention and treatment in an endemic area of Bangladesh. Adult slash and burn cultivators in two sub-districts of the Rangamati District were selected and interviewed. Four focus group discussions were conducted, and this was followed by a cross-sectional quantitative survey with 200 participants. RESULTS: The respondents' general knowledge about malaria transmission and modes of prevention and treatment was good. However, there were some gaps regarding knowledge about specific aspects of malaria transmission and in particular about the increased risk associated with their occupation. Despite a much-reduced incidence of malaria in the study area, the respondents perceived the disease as life-threatening and knew that it needs rapid attention from a health worker. Moreover, the specific services offered by the local community health workers for malaria diagnosis and treatment were highly appreciated. Finally, the use of insecticide-treated mosquito nets (ITN) was considered as important and this intervention was uniformly stated as the main malaria prevention method. CONCLUSIONS: The findings from this study on promising KAP characteristics in the slash and burn cultivator population are reassuring that the goal of malaria elimination by the year 2030 can be achieved in Bangladesh.

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.

Malaria training for community health workers in the setting of elimination: a qualitative study from China.

BACKGROUND: Continuous training of health workers is a key intervention to maintain their good performance and keep their vigilance during malaria elimination programmes. However, countries progressing toward malaria elimination have a largely decreased malaria disease burden, less frequent exposure of health workers to malaria patients, and new challenges in the epidemiology of the remaining malaria cases. Moreover, competing health priorities and usually a decline in resources and in political commitment also pose challenges to the elimination programme. As a consequence, the acceptability, sustainability, and impact of malaria training and education programmes face challenges. However, little is known of the perceptions and expectations of malaria training and education programmes of health workers being engaged in countries with malaria elimination programmes. METHODS: This qualitative study provides information on perceptions and expectations of health workers of malaria training programmes from China, which aims to malaria elimination by the year 2020. This study was embedded into a larger study on the challenges and lessons learned during the malaria surveillance strategy in China, involving 42 interviews with malaria experts, health staff, laboratory practitioners, and village doctors at the provincial, city, county, township, and village levels from Gansu province (northwestern China) and Jiangsu province (southeastern China). RESULTS: In the context of an increasing number of imported malaria cases in China, the majority of respondents emphasized the necessity and importance of such programmes and complained about a decreasing frequency of training courses. Moreover, they called for innovative strategies to improve the implementation and sustainability of the malaria training programmes until the elimination goal has been achieved. Perceptions and expectations of health workers from different health centres were quite different. Health workers from higher-level facilities were more concerned about technical training aspects, while health workers from periphery of the health system expected to receive more training on field work coordination and on specific public health actions with regard to case detection and focus investigation. CONCLUSIONS: There is need to guarantee an ongoing good training of health workers in China on malaria aspects until the year 2020 and probably beyond.

Differential activity of methylene blue against erythrocytic and hepatic stages of Plasmodium.

BACKGROUND: In the context of malaria elimination/eradication, drugs that are effective against the different developmental stages of the parasite are highly desirable. The oldest synthetic anti-malarial drug, the thiazine dye methylene blue (MB), is known for its activity against Plasmodium blood stages, including gametocytes. The aim of the present study was to investigate a possible effect of MB against malaria parasite liver stages. METHODS: MB activity was investigated using both in vitro and in vivo models. In vitro assays consisted of testing MB activity on Plasmodium falciparum, Plasmodium cynomolgi and Plasmodium yoelii parasites in human, simian or murine primary hepatocytes, respectively. MB in vivo activity was evaluated using intravital imaging in BALB/c mice infected with a transgenic bioluminescent P. yoelii parasite line. The transmission-blocking activity of MB was also addressed using mosquitoes fed on MB-treated mice. RESULTS: MB shows no activity on Plasmodium liver stages, including hypnozoites, in vitro in primary hepatocytes. In BALB/c mice, MB has moderate effect on P. yoelii hepatic development but is highly effective against blood stage growth. MB is active against gametocytes and abrogates parasite transmission from mice to mosquitoes. CONCLUSION: While confirming activity of MB against both sexual and asexual blood stages, the results indicate that MB has only little activity on the development of the hepatic stages of malaria parasites.

Decreasing child mortality, spatial clustering and decreasing disparity in North-Western Burkina Faso.

Within relatively small areas, there exist high spatial variations of mortality between villages. In rural Burkina Faso, with data from 1993 to 1998, clusters of particularly high child mortality were identified in the population of the Nouna Health and Demographic Surveillance System (HDSS), a member of the INDEPTH Network. In this paper, we report child mortality with respect to temporal trends, spatial clustering and disparity in this HDSS from 1993 to 2012. Poisson regression was used to describe village-specific child mortality rates and time trends in mortality. The spatial scan statistic was used to identify villages or village clusters with higher child mortality. Clustering of mortality in the area is still present, but not as strong as before. The disparity of child mortality between villages has decreased. The decrease occurred in the context of an overall halving of child mortality in the rural area of Nouna HDSS between 1993 and 2012. Extrapolated to the Millennium Development Goals target period 1990-2015, this yields an estimated reduction of 54%, which is not too far off the aim of a two-thirds reduction.

Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomized controlled trial in Burkina Faso.

BACKGROUND: Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties. METHODS: Three days of treatment with artesunate (AS)-amodiaquine (AQ) combined with MB was compared with AS-AQ treatment in a randomized controlled phase IIb study; the study included 221 children aged 6-59 months with uncomplicated falciparum malaria in Burkina Faso. The primary end point was gametocyte prevalence during follow-up, as determined by microscopy and real-time quantitative nucleic acid sequence-based amplification (QT-NASBA). RESULTS: The gametocyte prevalence of Plasmodium falciparum at baseline was 3.6% (microscopy) and 97% (QT-NASBA). It was significantly lower in the AS-AQ-MB than in the AS-AQ group on day 7 of follow-up (microscopy, 1.2% vs 8.9% [P < .05]; QT-NASBA, 36.7% vs 63.3% [P < .001]). Hemoglobin values were significantly lower in the AS-AQ-MB group than in the AS-AQ group at days 2 and 7 of follow-up. Vomiting of the study medication occurred significantly more frequently in the AS-AQ-MB group. CONCLUSIONS: The combination of MB with an artemisinin-based combination therapy has been confirmed to be effective against the gametocytes of P. falciparum. MB-based combinations need to be compared with primaquine-based combinations, preferably using MB in an improved pediatric formulation. Clinical Trials Registration: NCT01407887.

An insecticide-treated bed-net campaign and childhood malaria in Burkina Faso.

OBJECTIVE: To investigate if the first national insecticide-treated bed-net campaign in Burkina Faso, done in 2010, was followed by a decrease in childhood malaria in a district with high baseline transmission of the disease. METHODS: We obtained data on the prevalence of Plasmodium falciparum parasitaemia in children aged 2 weeks to 36 months from malaria surveys in 2009 and 2011. We assessed morbidity in children younger than 5 years by comparing data from the Nouna health district's health management information system before and after the campaign in 2010. We analysed mortality data from 2008 to 2012 from Nouna's health and demographic surveillance system. FINDINGS: The bed-net campaign was associated with an increase in the reported use of insecticide-treated nets. In 2009, 73% (630/869) of children reportedly slept under nets. In 2011, 92% (449/487) did. The campaign had no effect on the proportion of young children with P. falciparum parasitaemia after the rainy season; 52% (442/858) in 2009 and 53% (263/499) in 2011. Cases of malaria increased markedly after the campaign, as did the number of children presenting with other diseases. The campaign was not associated with any changes in child mortality. CONCLUSION: The 2010 insecticide-treated net campaign in Burkina Faso was not associated with a decrease in care-seeking for malaria or all-cause mortality in children younger than 5 years. The most likely explanation is the high coverage of nets in the study area before the campaign which could have had an effect on mosquito vectors, limiting the campaign's impact.