Safety and upscaling of remote consulting for long-term conditions in primary health care in Nigeria and Tanzania (REaCH trials): stepped-wedge trials of training, mobile data allowance, and implementation.

BACKGROUND: In-person health care poses risks to health workers and patients during pandemics. Remote consultations can mitigate these risks. The REaCH intervention comprised training and mobile data allowance provision for mobile phones to support remotely delivered primary care in Africa compared with no training and mobile data allowance. The aim of this study was to estimate the effects of REaCH among adults with non-communicable diseases on remote and face-to-face consultation rates, patient safety, and trustworthiness of consultations. METHODS: In these two independent stepped-wedge cluster randomised controlled trials, we enrolled 20 primary care clusters in each of two settings (Oyo State, Nigeria, and Morogoro Region, Tanzania). Eligible clusters had 100 or more patients with diabetes, hypertension, and cardiovascular or pulmonary disease employing five health workers. Clusters were computer-randomised to one of ten (Nigeria) or one of seven (Tanzania) sequences to receive the REaCH intervention. Only outcome assessors were masked. Primary outcomes were consultation, prescription, and investigation rates, and trustworthiness collected monthly for 12 months (Nigeria) and 9 months (Tanzania) from open cohorts. Ten randomly sampled consulting patients per cluster-month completed patient reported outcome measures. This trial was registered with ISRCTN, ISRCTN17941313. FINDINGS: Overall, 40 clusters comprising 8776 (Nigeria) and 3246 (Tanzania) patients' open cohort data were analysed (6377 [72·7%] of 8776 females in Nigeria, and 2235 [68·9%] of 3246 females in Tanzania). The mean age of the participants was 55·3 years (SD 13·9) in Nigeria and 59·2 years (14·2) in Tanzania. In Nigeria, no evidence of change in face-to-face consulting rate was observed (rate ratio [RR] 1·06, 95% CI 0·98 to 1·09; p=0·16); however, remote consultations increased four-fold (4·44, 1·34 to >10; p=0·01). In Tanzania, face-to-face (0·94, 0·61 to 1·67; p=0·99) and remote consulting rates (1·17, 0·56 to 5·57; p=0·39) were unchanged. There was no evidence of difference in prescribing rates (Nigeria: 1·05, 0·60 to 1·14; p=0·23; Tanzania: 0·92, 0·60 to 1·67; p=0·97), investigation rates (Nigeria: 1·06, 0·23 to 2·12; p=0·49; Tanzania: 1·15, 0·35 to 1·64; 0·58) or trustworthiness scores (Nigeria: mean difference 0·05, 95% CI -0·45 to 0·42; p=0·89; Tanzania: 0·07, -0·15 to 0·76; p=0·70). INTERPRETATION: REaCH can be implemented and could improve intervention versus control health-care access. Remote consultations appear safe and trustworthy, supporting universal health coverage. FUNDING: The UK Research and Innovation Collective Fund. TRANSLATIONS: For the Swahili and Yoruba translations of the abstract see Supplementary Materials section.

Remote Consulting in Primary Health Care in Low- and Middle-Income Countries: Feasibility Study of an Online Training Program to Support Care Delivery During the COVID-19 Pandemic.

BACKGROUND: Despite acceleration of remote consulting throughout the COVID-19 pandemic, many health care professionals are practicing without training to offer teleconsultation to their patients. This is especially challenging in resource-poor countries, where the telephone has not previously been widely used for health care. OBJECTIVE: As the COVID-19 pandemic dawned, we designed a modular online training program for REmote Consulting in primary Health care (REaCH). To optimize upscaling of knowledge and skills, we employed a train-the-trainer approach, training health workers (tier 1) to cascade the training to others (tier 2) in their locality. We aimed to determine whether REaCH training was acceptable and feasible to health workers in rural Tanzania to support their health care delivery during the pandemic. METHODS: We developed and pretested the REaCH training program in July 2020 and created 8 key modules. The program was then taught remotely via Moodle and WhatsApp (Meta Platforms) to 12 tier 1 trainees and cascaded to 63 tier 2 trainees working in Tanzania's rural Ulanga District (August-September 2020). We evaluated the program using a survey (informed by Kirkpatrick's model of evaluation) to capture trainee satisfaction with REaCH, the knowledge gained, and perceived behavior change; qualitative interviews to explore training experiences and views of remote consulting; and documentary analysis of emails, WhatsApp texts, and training reports generated through the program. Quantitative data were analyzed using descriptive statistics. Qualitative data were analyzed thematically. Findings were triangulated and integrated during interpretation. RESULTS: Of the 12 tier 1 trainees enrolled in the program, all completed the training; however, 2 (17%) encountered internet difficulties and failed to complete the evaluation. In addition, 1 (8%) opted out of the cascading process. Of the 63 tier 2 trainees, 61 (97%) completed the cascaded training. Of the 10 (83%) tier 1 trainees who completed the survey, 9 (90%) would recommend the program to others, reported receiving relevant skills and applying their learning to their daily work, demonstrating satisfaction, learning, and perceived behavior change. In qualitative interviews, tier 1 and 2 trainees identified several barriers to implementation of remote consulting, including lacking digital infrastructure, few resources, inflexible billing and record-keeping systems, and limited community awareness. The costs of data or airtime emerged as the greatest immediate barrier to supporting both the upscaling of REaCH training and subsequently the delivery of safe and trustworthy remote health care. CONCLUSIONS: The REaCH training program is feasible, acceptable, and effective in changing trainees' behavior. However, government and organizational support is required to facilitate the expansion of the program and remote consulting in Tanzania and other low-resource settings.

Mobile consulting as an option for delivering healthcare services in low-resource settings in low- and middle-income countries: A mixed-methods study.

OBJECTIVE: Remote or mobile consulting is being promoted to strengthen health systems, deliver universal health coverage and facilitate safe clinical communication during coronavirus disease 2019 and beyond. We explored whether mobile consulting is a viable option for communities with minimal resources in low- and middle-income countries. METHODS: We reviewed evidence published since 2018 about mobile consulting in low- and middle-income countries and undertook a scoping study (pre-coronavirus disease) in two rural settings (Pakistan and Tanzania) and five urban slums (Kenya, Nigeria and Bangladesh), using policy/document review, secondary analysis of survey data (from the urban sites) and thematic analysis of interviews/workshops with community members, healthcare workers, digital/telecommunications experts, mobile consulting providers, and local and national decision-makers. Project advisory groups guided the study in each country. RESULTS: We reviewed four empirical studies and seven reviews, analysed data from 5322 urban slum households and engaged with 424 stakeholders in rural and urban sites. Regulatory frameworks are available in each country. Mobile consulting services are operating through provider platforms (n = 5-17) and, at the community level, some direct experience of mobile consulting with healthcare workers using their own phones was reported - for emergencies, advice and care follow-up. Stakeholder willingness was high, provided challenges are addressed in technology, infrastructure, data security, confidentiality, acceptability and health system integration. Mobile consulting can reduce affordability barriers and facilitate care-seeking practices. CONCLUSIONS: There are indications of readiness for mobile consulting in communities with minimal resources. However, wider system strengthening is needed to bolster referrals, specialist services, laboratories and supply chains to fully realise the continuity of care and responsiveness that mobile consulting services offer, particularly during/beyond coronavirus disease 2019.

Occurrence of 4 Dengue Virus Serotypes and Chikungunya Virus in Kilombero Valley, Tanzania, During the Dengue Outbreak in 2018.

BACKGROUND: Dengue and Chikungunya viruses can cause large-scale epidemics, with attack rates of up to 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent in 2018 and 2019, mostly affecting the coastal areas. Despite the importance of these viruses, there is limited knowledge on the epidemiology of dengue (DENV) and Chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero Valley, Tanzania. METHODS: A cross-sectional study was conducted at Kibaoni Health Center in Kilombero Valley, Southeastern Tanzania, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled from the outpatient department. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time reverse transcription polymerase chain reaction assays. RESULTS: Overall, 294 patients were recruited. Most were females (65%), and one-third of patients were aged 14-25 years. DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups during both the dry and rainy seasons. Although all 4 DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections. CONCLUSIONS: This study reveals the co-circulation of all 4 DENV serotypes and CHIKV in Kilombero. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. The occurrence of all serotypes suggests the possibility of severe clinical outcomes in future DENV epidemics in Tanzania.

High malaria parasitemia among outpatient febrile children in low endemic area, East-Central Tanzania in 2013.

OBJECTIVE: This study investigated the prevalence and distribution patterns of malaria in Kilosa district as part of non-malaria causes of febrile illnesses in children study. We enrolled febrile patients aged 2-13 years presenting at the outpatient department during the rainy and dry seasons, in 2013. For each participant, we tested for malaria parasites and identified parasite species using microscopy. We then calculated parasite density and estimated geometric mean parasite density. RESULTS: The overall malaria prevalence in febrile children was 23.7% (n = 609). Plasmodium falciparum accounted for 98.6% of malaria positives. There was a heterogeneous distribution of malaria cases among the 17 wards constituting the catchment area. A high proportion (69.4%, n = 144) of malaria positive individuals had high parasite densities. Individuals who were enrolled in the rainy season had higher geometric mean parasite density (15415.1 parasites/µl, 95% CI 10735.3-22134.9) compared to the dry season (6115.3 parasites/µl, 95% CI 4237.8-8824.6). The relatively high malaria prevalence recorded in Kilosa, an area considered low endemicity, calls for concerted effort in documenting malaria burden at fine geographical scales and tailor preventive and control strategies that target hotspots of high malaria transmission.

Mobile consulting (mConsulting) and its potential for providing access to quality healthcare for populations living in low-resource settings of low- and middle-income countries.

OBJECTIVE: The poorest populations of the world lack access to quality healthcare. We defined the key components of consulting via mobile technology (mConsulting), explored whether mConsulting can fill gaps in access to quality healthcare for poor and spatially marginalised populations (specifically rural and slum populations) of low- and middle-income countries, and considered the implications of its take-up. METHODS: We utilised realist methodology. First, we undertook a scoping review of mobile health literature and searched for examples of mConsulting. Second, we formed our programme theories and identified potential benefits and hazards for deployment of mConsulting for poor and spatially marginalised populations. Finally, we tested our programme theories against existing frameworks and identified published evidence on how and why these benefits/hazards are likely to accrue. RESULTS: We identified the components of mConsulting, including their characteristics and range. We discuss the implications of mConsulting for poor and spatially marginalised populations in terms of competent care, user experience, cost, workforce, technology, and the wider health system. CONCLUSIONS: For the many dimensions of mConsulting, how it is structured and deployed will make a difference to the benefits and hazards of its use. There is a lack of evidence of the impact of mConsulting in populations that are poor and spatially marginalised, as most research on mConsulting has been undertaken where quality healthcare exists. We suggest that mConsulting could improve access to quality healthcare for these populations and, with attention to how it is deployed, potential hazards for the populations and wider health system could be mitigated.

Factors Affecting Performance in Clinical Practice among Preservice Diploma Nursing Students in Northern Tanzania.

There is an increased call for improving the environment in which nursing students learn the clinical skills. Clinical practice in the clinical placement sites should allow students to apply their theoretical knowledge in a real environment, develop nursing skills and clinical reasoning, and observe and adapt the professional role. This study aimed at identifying the factors influencing performance in clinical practice among preservice diploma nursing students in Northern Tanzania. This study relied on a cross-sectional analysis of data collected from nursing schools in Northern Tanzania in which 208 (123 nursing students and 85 nurse tutors) participants were recruited in the study. Data was gathered using a self-administered questionnaire which collected information on sociodemographic characteristics and factors influencing clinical practice categorized in students' factors, hospital based factors, social-economic factors, and nurse tutors opinions assessed. Descriptive analyses and chi-square test were employed to understand the background information of the sample and association between variables. Majority of the nursing students (84.4%) agreed that clinical placement offers students adequate opportunity for clinical practical learning. Barriers to effective clinical learning was reported by 70.1% of the participants and the barriers include student factors such as lack of self-confidence and absenteeism, school factors such as improper supervision, and poor preparation of clinical instructors or clinical facility factors. We found a significant association between type of barrier and gender (chi-square 0.786, p=0.020). More male nursing students (62.1%) significantly reported unsupportive environment as a barrier and anxiety was more common in female nursing students (48.9%) (p=0.020). Reporting of barriers to effective clinical learning by students from different schools of nursing was not significant (P=0.696). In addition, age of participants did not have significant association with effective clinical practice (p=0.606). Student's factors and placement based factors played an important role to influence clinical learning experiences. Offering preclinical orientation, distributing and clarifying clinical learning objectives to students, and frequent visits and supervision of students in clinical area may improve student learning experience in clinical placement. In addition, tailoring the interventions to gender may improve learning experiences.

Prevalence of bacterial febrile illnesses in children in Kilosa district, Tanzania.

INTRODUCTION: Bacterial etiologies of non-malaria febrile illnesses have significantly become important due to high mortality and morbidity, particularly in children. Despite their importance, there are few reports on the epidemiology of these diseases in Tanzania, and the true burden of such illnesses remains unknown. This study aimed to identify the prevalence of leptospirosis, brucellosis, typhoid fever and urinary tract infections and their rate of co-infections with malaria. METHODS: A cross-sectional study was conducted at Kilosa district hospital in Tanzania for 6 months. Febrile children aged from 2-13 years were recruited from the outpatient department. Patients were screened by serological tests such as IgM and IgG ELISA, and microscopic agglutination test. RESULTS: A total of 370 patients were enrolled; of these 85 (23.0%) had malaria parasites, 43 (11.6%) had presumptive acute leptospirosis and 26/200 (13%) had confirmed leptospirosis. Presumptive acute brucellosis due to B. abortus was identified among 26 (7.0%) of patients while B. melitensis was detected in 57 (15.4%) of the enrolled patients. Presumptive typhoid fever due to S. Typhi was identified in thirty eight (10.3%) of the participants and 69 (18.6%) had urinary tract infections. Patients presented with similar symptoms; therefore, the identification of these diseases could not be done based on clinical ground alone. Co-infections between malaria and bacterial febrile illnesses were observed in 146 patients (39.5%). Although antibacterials and/or anti-malarials were prescribed in most patients, some patients did not receive the appropriate treatment. CONCLUSION: The study has underscored the importance of febrile bacterial diseases including zoonoses such as leptospirosis and brucellosis in febrile children, and thus such illnesses should be considered by clinicians in the differential diagnoses of febrile diseases. However, access to diagnostic tests for discrimination of febrile illnesses is needed. This would allow febrile patients to receive the correct diagnoses and facilitation of accurate and prompt treatment.

Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania.

INTRODUCTION: Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. METHODS: A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2-13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. RESULTS: A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35-3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. CONCLUSION: Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.

Self-medication with anti-malarials is a common practice in rural communities of Kilosa district in Tanzania despite the reported decline of malaria.

BACKGROUND: Self-medication has been widely practiced worldwide particularly in developing countries including Tanzania. In sub-Saharan Africa high incidences of malaria have contributed to self-medication with anti-malarial drugs. In recent years, there has been a gain in malaria control, which has led to decreased malaria transmission, morbidity and mortality. Therefore, understanding the patterns of self-medication during this period when most instances of fever are presumed to be due to non-malaria febrile illnesses is important. In this study, self-medication practice was assessed among community members and information on the habit of self-medication was gathered from health workers. METHODS: Twelve focus group discussions (FGD) with members of communities and 14 in-depth interviews (IDI) with health workers were conducted in Kilosa district, Tanzania. The transcripts were coded into different categories by MaxQDA software and then analysed through thematic content analysis. RESULTS: The study revealed that self-medication was a common practice among FGD participants. Anti-malarial drugs including sulphadoxine-pyrimethamine and quinine were frequently used by the participants for treatment of fever. Study participants reported that they visited health facilities following failure of self-medication or if there was no significant improvement after self-medication. The common reported reasons for self-medication were shortages of drugs at health facilities, long waiting time at health facilities, long distance to health facilities, inability to pay for health care charges and the freedom to choose the preferred drugs. CONCLUSION: This study demonstrated that self-medication practice is common among rural communities in the study area. The need for community awareness is emphasized for correct and comprehensive information about drawbacks associated with self-medication practices. Deliberate efforts by the government and other stakeholders to improve health care services, particularly at primary health care facilities will help to reduce self-medication practices.

Community knowledge and attitudes and health workers' practices regarding non-malaria febrile illnesses in eastern Tanzania.

INTRODUCTION: Although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. Recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. A number of non-malaria febrile illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection, leptospirosis, tick-borne relapsing fever and Q-fever have been reported in Tanzania. This study aimed at assessing the awareness of communities and practices of health workers on non-malaria febrile illnesses. METHODS: Twelve focus group discussions with members of communities and 14 in-depth interviews with health workers were conducted in Kilosa district, Tanzania. Transcripts were coded into different groups using MaxQDA software and analyzed through thematic content analysis. RESULTS: The study revealed that the awareness of the study participants on non-malaria febrile illnesses was low and many community members believed that most instances of fever are due to malaria. In addition, the majority had inappropriate beliefs about the possible causes of fever. In most cases, non-malaria febrile illnesses were considered following a negative Malaria Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti-malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic facilities for febrile illnesses including mRDTs were repeatedly reported as a major barrier to proper diagnosis and treatment of febrile patients. CONCLUSION: Our results emphasize the need for creating community awareness on other causes of fever apart from malaria. Based on our study, appropriate treatment of febrile patients will require inputs geared towards strengthening of diagnostic facilities, drugs availability and optimal staffing of health facilities.

Implications of bio-efficacy and persistence of insecticides when indoor residual spraying and long-lasting insecticide nets are combined for malaria prevention.

BACKGROUND: Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs) were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. METHODS: Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life®) and three IRS treatments (2 g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts). Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS) or wire balls (nets only). Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr) genes. RESULTS: IRS treatments killed ≥ 85% of mosquitoes exposed on palm ceilings and ≥ 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1-3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. Wild An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. CONCLUSIONS: In bioassays where sufficient contact with treated surfaces is assured, LLINs and IRS kill high proportions of susceptible An. arabiensis mosquitoes, though these efficacies decay gradually for LLINs and rapidly for IRS. It is, therefore, important to always add intact nets in sprayed houses, guaranteeing protection even after the IRS decays, and to ensure accurate timing, quality control and regular re-spraying in IRS programmes. By contrast, adding IRS in houses with intact LLINs is unlikely to improve protection relative to LLINs alone, since there is no guarantee that unfed vectors would rest long enough on the sprayed surfaces, and because of the rapid IRS decay. However, there is need to clarify these effects using data from observations of free flying mosquitoes in huts. Physiological susceptibility of An. arabiensis in the area remains 100% against DDT, but is slightly reduced against pyrethroids, necessitating caution over possible spread of resistance. The loss of LLIN toxicity, particularly Olyset® nets suggests that protection offered by these nets against An. arabiensis may be primarily due to physical bite prevention rather than insecticidal efficacy.

Impact of promoting longer-lasting insecticide treatment of bed nets upon malaria transmission in a rural Tanzanian setting with pre-existing high coverage of untreated nets.

BACKGROUND: The communities of Namawala and Idete villages in southern Tanzania experienced extremely high malaria transmission in the 1990s. By 2001-03, following high usage rates (75% of all age groups) of untreated bed nets, a 4.2-fold reduction in malaria transmission intensity was achieved. Since 2006, a national-scale programme has promoted the use of longer-lasting insecticide treatment kits (consisting of an insecticide plus binder) co-packaged with all bed nets manufactured in the country. METHODS: The entomological inoculation rate (EIR) was estimated through monthly surveys in 72 houses randomly selected in each of the two villages. Mosquitoes were caught using CDC light traps placed beside occupied bed nets between January and December 2008 (n = 1,648 trap nights). Sub-samples of mosquitoes were taken from each trap to determine parity status, sporozoite infection and Anopheles gambiae complex sibling species identity. RESULTS: Compared with a historical mean EIR of approximately 1400 infectious bites/person/year (ib/p/y) in 1990-94; the 2008 estimate of 81 ib/p/y represents an 18-fold reduction for an unprotected person without a net. The combined impact of longer-lasting insecticide treatments as well as high bed net coverage was associated with a 4.6-fold reduction in EIR, on top of the impact from the use of untreated nets alone. The scale-up of bed nets and subsequent insecticidal treatment has reduced the density of the anthropophagic, endophagic primary vector species, Anopheles gambiae sensu stricto, by 79%. In contrast, the reduction in density of the zoophagic, exophagic sibling species Anopheles arabiensis was only 38%. CONCLUSION: Insecticide treatment of nets reduced the intensity of malaria transmission in addition to that achieved by the untreated nets alone. Impacts were most pronounced against the highly anthropophagic, endophagic primary vector, leading to a shift in the sibling species composition of the A. gambiae complex.

The affinity of the FimH fimbrial adhesin is receptor-driven and quasi-independent of Escherichia coli pathotypes.

Type-1 fimbriae are important virulence factors for the establishment of Escherichia coli urinary tract infections. Bacterial adhesion to the high-mannosylated uroplakin Ia glycoprotein receptors of bladder epithelium is mediated by the FimH adhesin. Previous studies have attributed differences in mannose-sensitive adhesion phenotypes between faecal and uropathogenic E. coli to sequence variation in the FimH receptor-binding domain. We find that FimH variants from uropathogenic, faecal and enterohaemorrhagic isolates express the same specificities and affinities for high-mannose structures. The only exceptions are FimHs from O157 strains that carry a mutation (Asn135Lys) in the mannose-binding pocket that abolishes all binding. A high-mannose microarray shows that all substructures are bound by FimH and that the largest oligomannose is not necessarily the best binder. Affinity measurements demonstrate a strong preference towards oligomannosides exposing Manalpha1-3Man at their non-reducing end. Binding is further enhanced by the beta1-4-linkage to GlcNAc, where binding is 100-fold better than that of alpha-d-mannose. Manalpha1-3Manbeta1-4GlcNAc, a major oligosaccharide present in the urine of alpha-mannosidosis patients, thus constitutes a well-defined FimH epitope. Differences in affinities for high-mannose structures are at least 10-fold larger than differences in numbers of adherent bacteria between faecal and uropathogenic strains. Our results imply that the carbohydrate expression profile of targeted host tissues and of natural inhibitors in urine, such as Tamm-Horsfall protein, are stronger determinants of adhesion than FimH variation.