Effectiveness of malaria chemoprevention in the first two years of life in Cameroon and Côte d'Ivoire compared to standard of care: study protocol for a population-based prospective cohort impact evaluation study.

BACKGROUND: Perennial malaria chemoprevention (PMC) is a chemoprevention strategy endorsed by the World Health Organization (WHO) and is increasingly being adopted by National Malaria Programmes. PMC aims to reduce morbidity and mortality caused by malaria and anaemia in in young children through provision of antimalarial drugs at routine contact points with the local health system. This study aims to evaluate the impact of the programmatically-implemented country-tailored PMC programmes targeting children up to two years of age using sulfadoxine-pyrimethamine (SP) on the incidence of malaria and anaemia in children in Cameroon and Côte d'Ivoire. METHODS: We will assess the impact of PMC using passive and active monitoring of a prospective observational cohort of children up to 36 months of age at recruitment in selected study sites in Cameroon and Côte d'Ivoire. The primary and secondary outcomes include malaria, anaemia and malnutrition incidence. We will also conduct a time-series analysis of passively detected malaria and anaemia cases comparing the periods before and after PMC introduction. This study is powered to detect a 30% and 40% reduction of malaria incidence compared to the standard of care in Cameroon and Côte d'Ivoire, respectively. DISCUSSION: This multi-country study aims to provide evidence of the effectiveness of PMC targeting children in the first two years of life on malaria and anaemia and will provide important information to inform optimal operationalization and evaluation of this strategy. TRIAL REGISTRATION: Cameroon - NCT05889052; Côte d'Ivoire - NCT05856357.

Patients with positive malaria tests not given artemisinin-based combination therapies: a research synthesis describing under-prescription of antimalarial medicines in Africa.

BACKGROUND: There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. METHODS: Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007-2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. RESULTS: Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of < 5-year-olds not prescribed ACT ranged up to 41.8% across sites. The odds of not being prescribed an ACT were 2-32 times higher for patients in settings with lower-transmission intensity (using test positivity as a proxy) compared to areas of higher transmission. mRDT-positive children in low-transmission settings were especially likely not to be prescribed ACT, with proportions untreated up to 70%. Of the 7426 mRDT-positive patients not prescribed an ACT, 4121 (55.5%) were prescribed other, non-recommended non-ACT antimalarial medications, and the remainder (44.5%) were prescribed no antimalarial. CONCLUSIONS: In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children < 5 years and those in low-transmission settings, were most likely to not be prescribed antimalarials, and young children in low-transmission settings were least likely to be treated for malaria. This major public health risk must be addressed in training and practice. TRIAL REGISTRATION: Reported in individual primary studies.

Adherence and acceptability of community-based distribution of micronutrient powders in Southern Mali.

Home fortification with micronutrient powders (MNP) has been shown to reduce anaemia, with high overall acceptability and adherence, but there is limited evidence from West Africa. Around 80% of children younger than 5 years are anaemic in Mali, and new interventions are needed. This paper reports on the adherence and acceptability of a community-led MNP intervention targeting children aged 6-59 months in Southern Mali. The MNP were delivered by a multidisciplinary group of community volunteers using community-based preschools, cooking demonstrations, and traditional communication networks to promote MNP, nutrition, hygiene, and child stimulation. The MNP were delivered alongside early childhood development interventions and seasonal malaria chemoprevention. Adherence and acceptability were evaluated through two cross-sectional surveys in 2014 and 2016 and a qualitative evaluation in 2015. Over 80% of parents reported ever having given MNP to their child, with 65% having given MNP for four or more days in the last week. Likely contributors to uptake include: perceived positive changes in the children following MNP use, the selection of a food vehicle that was already commonly given to children (morning porridge or bouillie) and the community driven, decentralized and integrated delivery approach. These findings support recommendations from recent reviews of MNP implementation to use community-based delivery approaches and behaviour change components.

Caregivers' compliance with referral advice: evidence from two studies introducing mRDTs into community case management of malaria in Uganda.

BACKGROUND: Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. METHODS: Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010-July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers' referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. RESULTS: CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings < 10% of caregivers complied with referral advice. In the moderate-to-high transmission setting compliance was higher if children were tested with mRDT compared to children who were not tested with mRDT. In both settings, nearly all children treated with pre-referral rectal artesunate failed to comply with referral and compliance was independently associated with factors such as health centre distance and day of referral by a CHW. In the moderate-to-high transmission setting, time of presentation, severity of referral were also associated with compliance, whilst in the low-transmission setting, compliance was low if an ACT was prescribed. CONCLUSIONS: This analysis suggests there are several barriers to comply with CHWs referral advice by caregivers. This is concerning for children who received rectal artesunate. As CHW programmes continue scale-up, barriers to referral compliance need to be addressed to ensure a continuum of care from the community to the health centre. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov. Identifier NCT01048801 , 13th January 2010.

Anti-malarial medicine quality field studies and surveys: a systematic review of screening technologies used and reporting of findings.

BACKGROUND: Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a snap shot of medicine quality in a specific geographical area. This review presents an overview of the screening tests typically employed in surveys to assess anti-malarial medicine quality, summarizes the analytical methods used, how findings have been reported and proposes a reporting template for future studies. METHODS: A systematic search of the peer-reviewed and grey literature available in the public domain (including national and multi-national medicine quality surveys) covering the period 1990-2016 was undertaken. Studies were included if they had used screening techniques to assess the quality of anti-malarial medicines. As no standardized set of guidelines for the methodology and reporting of medicine quality surveys exist, the included studies were assessed for their standard against a newly proposed list of criteria. RESULTS: The titles and abstracts of 4621 records were screened and only 39 were found to meet the eligibility criteria. These 39 studies utilized visual inspection, disintegration, colorimetry and Thin Layer Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF) MiniLab® or as individual tests. Overall, 30/39 studies reported employing confirmatory testing described in international pharmacopeia to verify the quality of anti-malarials post assessment by a screening test. The authors assigned scores for the 23 criteria for the standard of reporting of each study. CONCLUSIONS: There is considerable heterogeneity in study design and inconsistency in reporting of field surveys of medicine quality. A lack of standardization in the design and reporting of studies of medicine quality increases the risk of bias and error, impacting on the generalizability and reliability of study results. The criteria proposed for reporting on the standard of studies in this review can be used in conjunction with existing medicine quality survey guidelines as a checklist for designing and reporting findings of studies. The review protocol has been registered with PROSPERO (CRD42015026782).

Referral of children seeking care at private health facilities in Uganda.

BACKGROUND: In Uganda, referral of sick children seeking care at public health facilities is poor and widely reported. However, studies focusing on the private health sector are scanty. The main objective of this study was to assess referral practices for sick children seeking care at private health facilities in order to explore ways of improving treatment and referral of sick children in this sector. METHODS: A survey was conducted from August to October 2014 in Mukono district, central Uganda. Data was collected using a structured questionnaire supplemented by Focus Group Discussions and Key Informant interviews with private providers and community members. RESULTS: A total of 241 private health facilities were surveyed; 170 (70.5%) were registered drug shops, 59 (24.5%) private clinics and 12 (5.0%) pharmacies. Overall, 104/241 (43.2%) of the private health facilities reported that they had referred sick children to higher levels of care in the two weeks prior to the survey. The main constraints to follow referral advice as perceived by caretakers were: not appreciating the importance of referral, gender-related decision-making and negotiations at household level, poor quality of care at referral facilities, inadequate finances at household level; while the perception that referral leads to loss of prestige and profit was a major constraint to private providers. CONCLUSION: In conclusion, the results show that referral of sick children at private health facilities faces many challenges at provider, caretaker, household and community levels. Thus, interventions to address constraints to referral of sick children are urgently needed.

Comparison of the capacity between public and private health facilities to manage under-five children with febrile illnesses in Uganda.

BACKGROUND: Public health facilities are usually the first to receive interventions compared to private facilities, yet majority of health seeking care is first done with the latter. This study compared the capacity to manage acute febrile illnesses in children below 5 years in private vs public health facilities in order to design interventions to improve quality of care. METHODS: A survey was conducted within 57 geographical areas (parishes), from August to October 2014 in Mukono district, central Uganda. The survey comprised both facility and health worker assessment. Data were collected on drug stocks, availability of treatment guidelines, diagnostic equipment, and knowledge in management of malaria, pneumonia and diarrhoea, using a structured questionnaire. RESULTS: A total of 53 public and 241 private health facilities participated in the study. While similar proportions of private and public health facilities stocked Coartem, the first-line anti-malarial drug, (98 vs 95%, p = 0.22), significantly more private than public health facilities stocked quinine (85 vs 53%, p < 0.01). Stocks of obsolete anti-malarial drugs, such as chloroquine, were reported in few public and private facilities (3.7 vs 12.5%, p = 0.06). Stocks of antibiotics-amoxycillin and gentamycin were similar in both sectors (≥90% for amoxicillin; ≥50 for gentamycin). Training in malaria was reported by 65% of public health facilities vs 56% in the private sector, p = 0.25), while, only 21% in the public facility and 12% in the private facilities, p = 0.11, reported receiving training in pneumonia. Only 55% of public facilities had microscopes. Malaria treatment guidelines were significantly lacking in the private sector, p = 0.01. Knowledge about first-line management of uncomplicated malaria, pneumonia and diarrhoea was significantly better in the public facilities compared to the private ones, though still sub-optimal. CONCLUSION: Deficiencies of equipment, supplies and training exist even in public health facilities. In order to significantly improve the capacity to handle acute febrile illness among children under five, training in proper case management, availability of supplies and diagnostics need to be addressed in both sectors.

Cost analysis of a school-based comprehensive malaria program in primary schools in Sikasso region, Mali.

BACKGROUND: The expansion of malaria prevention and control to school-aged children is receiving increasing attention, but there are still limited data on the costs of intervention. This paper analyses the costs of a comprehensive school-based intervention strategy, delivered by teachers, that included participatory malaria educational activities, distribution of long lasting insecticide-treated nets (LLIN), and Intermittent Parasite Clearance in schools (IPCs) in southern Mali. METHODS: Costs were collected alongside a randomised controlled trial conducted in 80 primary schools in Sikasso Region in Mali in 2010-2012. Cost data were compiled between November 2011 and March 2012 for the 40 intervention schools (6413 children). A provider perspective was adopted. Using an ingredients approach, costs were classified by cost category and by activity. Total costs and cost per child were estimated for the actual intervention, as well as for a simpler version of the programme more suited for scale-up by the government. Univariate sensitivity analysis was performed. RESULTS: The economic cost of the comprehensive intervention was estimated to $10.38 per child (financial cost $8.41) with malaria education, LLIN distribution and IPCs costing $2.13 (20.5%), $5.53 (53.3%) and $2.72 (26.2%) per child respectively. Human resources were found to be the key cost driver, and training costs were the greatest contributor to overall programme costs. Sensitivity analysis showed that an adapted intervention delivering one LLIN instead of two would lower the economic cost to $8.66 per child; and that excluding LLIN distribution in schools altogether, for example in settings where malaria control already includes universal distribution of LLINs at community-level, would reduce costs to $4.89 per child. CONCLUSIONS: A comprehensive school-based control strategy may be a feasible and affordable way to address the burden of malaria among schoolchildren in the Sahel.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/µl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.

Community health workers adherence to referral guidelines: evidence from studies introducing RDTs in two malaria transmission settings in Uganda.

BACKGROUND: Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline. METHODS: A secondary analysis was undertaken of data collected during two cluster-randomized trials conducted between January 2010 and July 2011, one in a moderate-to-high malaria transmission setting and the other in a low malaria transmission setting. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) and recognize symptoms in children that required immediate referral to the nearest health centre. Intervention arm CHWs had additional training on how to conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria using clinical signs and symptoms. CHW treatment registers were reviewed to identify children eligible for referral according to training guidelines (temperature of ≥38.5 °C), to assess whether CHWs adhered to the guidelines and referred them. Factors associated with adherence were examined with logistic regression models. RESULTS: CHWs failed to refer 58.8% of children eligible in the moderate-to-high transmission and 31.2% of children in the low transmission setting. CHWs using RDTs adhered to the referral guidelines more frequently than CHWs not using RDTs (moderate-to-high transmission: 50.1 vs 18.0%, p = 0.003; low transmission: 88.5 vs 44.1%, p < 0.001). In both settings, fewer than 20% of eligible children received pre-referral treatment with rectal artesunate. Children who were prescribed ACT were very unlikely to be referred in both settings (97.7 and 73.3% were not referred in the moderate-to-high and low transmission settings, respectively). In the moderate-to-high transmission setting, day and season of visit were also associated with the likelihood of adherence to the referral guidelines, but not in the low transmission setting. CONCLUSIONS: CHW adherence to referral guidelines was poor in both transmission settings. However, training CHWs to use RDT improved correct referral of children with a high fever compared to a presumptive diagnosis using sign and symptoms. As many countries scale up CHW programmes, routine monitoring of reported data should be examined carefully to assess whether CHWs adhere to referral guidelines and take remedial actions where required.

Treatment and prevention of malaria in pregnancy in the private health sector in Uganda: implications for patient safety.

BACKGROUND: Malaria in pregnancy is a major public health problem in Uganda; and it is the leading cause of anaemia among pregnant women and low birth weight in infants. Previous studies have noted poor quality of care in the private sector. Thus there is need to explore ways of improving quality of care in the private sector that provides almost a half of health services in Uganda. METHODS: A survey was conducted from August to October 2014 within 57 parishes in Mukono district, central Uganda. The selected parishes had a minimum of 200 households and at least one registered drug shop, pharmacy or private clinic. Data was collected using a structured questionnaire targeting one provider who was found on duty in each selected private health facility and consented to the study. The main variables were: provider characteristics, previous training received, type of drugs stocked, treatment and prevention practices for malaria among pregnant women. The main study outcome was the proportion of private health facilities who prescribe treatment of fever among pregnant women as recommended in the guidelines. RESULTS: A total of 241 private health facilities were surveyed; 70.5 % were registered drug shops, 24.5 % private clinics and 5.0 % pharmacies. Treatment of fever among pregnant women in accordance with the national treatment guidelines was poor: 40.7 % in private clinics, decreasing to 28.2 % in drug shops and 16.7 % at pharmacies. Anti-malarial monotherapies sulphadoxine-pyrimethamine and quinine were commonly prescribed, often without consideration of gestational age. The majority of providers (>75 %) at all private facilities prescribed SP for intermittent preventive treatment but artemisinin-based combination therapy was prescribed: 8.3, 6.9 and 8.3 % respectively at drug shops, private clinics and pharmacies for prevention of malaria in pregnancy. Few facilities had malaria treatment guidelines; (44.1 % of private clinics, 17.9 % of drug shops, and 41.7 % at pharmacies. Knowledge of people at risk of malaria, P = 0.02 and availability of malaria treatment guidelines, P = 0.03 were the factors that most influenced correct treatment of fever in pregnancy. CONCLUSION: Treatment of fever during pregnancy was poor in this study setting. These data highlight the need to develop interventions to improve patient safety and quality of care for pregnant women in the private health sector in Uganda.

Assessing the potential of rural and urban private facilities in implementing child health interventions in Mukono district, central Uganda-a cross sectional study.

BACKGROUND: Private facilities are the first place of care seeking for many sick children. Involving these facilities in child health interventions may provide opportunities to improve child welfare. The objective of this study was to assess the potential of rural and urban private facilities in diagnostic capabilities, operations and human resource in the management of malaria, pneumonia and diarrhoea. METHODS: A survey was conducted in pharmacies, private clinics and drug shops in Mukono district in October 2014. An assessment was done on availability of diagnostic equipment for malaria, record keeping, essential drugs for the treatment of malaria, pneumonia and diarrhoea; the sex, level of education, professional and in-service training of the persons found attending to patients in these facilities. A comparison was made between urban and rural facilities. Univariate and bivariate analysis was done. RESULTS: A total of 241 private facilities were assessed with only 47 (19.5 %) being in rural areas. Compared to urban areas, rural private facilities were more likely to be drug shops (OR 2.80; 95 % CI 1.23-7.11), less likely to be registered (OR 0.31; 95 % CI 0.16-0.60), not have trained clinicians, less likely to have people with tertiary education (OR 0.34; 95 % CI 0.17-0.66) and less likely to have zinc tablets (OR 0.38; 95 % CI 0.19-0.78). In both urban and rural areas, there was low usage of stock cards and patient registers. About half of the facilities in both rural and urban areas attended to at least one sick child in the week prior to the interview. CONCLUSION: There were big gaps between rural and urban private facilities with rural ones having less trained personnel and less zinc tablets' availability. In both rural and urban areas, record keeping was low. Child health interventions need to build capacity of private facilities with special focus on rural areas where child mortality is higher and capacity of facilities lower.

Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda: lessons learned and policy implications.

BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons learned and policy implications. RESULTS: Introducing RDTs into drug shops was feasible. To scale-up this intervention however, drug shop practices need to be regulated since the registration process was not clear, supervision was inadequate and record keeping was poor. Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome, but at evaluation this was not found to be a constraint. This presents an important lesson for introducing health management information system into drug shops. Involving stakeholders, especially the district health team, in the design was important for ownership and sustainability. The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions. CONCLUSION: Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy. It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector.

Malaria in school-age children in Africa: an increasingly important challenge.

School-age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school-age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school-age children are presented and evidence that malaria adversely effects school performance is reviewed. Long-lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school-age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school-age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school-age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school-age children.

Invasive Anopheles stephensi in Africa: insights from Asia.

Anopheles stephensi is a highly competent urban malaria vector species, endemic in South Asia and the Persian Gulf, which has colonised eight countries in sub-Saharan Africa (SSA) since 2013 and is now spreading uncontrollably. In urban areas of Africa, where malaria transmission has previously been low or non-existent, the invasion of An. stephensi represents a significant problem, particularly to immunologically naïve populations. Despite this rapidly advancing threat, there is a paucity of information regarding the bionomics of An. stephensi in SSA. Here, we offer a critical synthesis of literature from An. stephensi's native range, focusing on the future of An. stephensi in a rapidly urbanising Africa, and highlighting key questions that warrant prioritisation by the global malaria vector control community.

Entomological surveys and insecticide susceptibility profile of Aedes aegypti during the dengue outbreak in Sao Tome and Principe in 2022.

BACKGROUND: The first dengue outbreak in Sao Tome and Principe was reported in 2022. Entomological investigations were undertaken to establish the typology of Aedes larval habitats, the distribution of Ae. aegypti and Ae. albopictus, the related entomological risk and the susceptibility profile of Ae. aegypti to insecticides, to provide evidence to inform the outbreak response. METHODOLOGY/PRINCIPAL FINDINGS: Entomological surveys were performed in all seven health districts of Sao Tome and Principe during the dry and rainy seasons in 2022. WHO tube and synergist assays using piperonyl butoxide (PBO) and diethyl maleate (DEM) were carried out, together with genotyping of F1534C/V1016I/V410L mutations in Ae. aegypti. Aedes aegypti and Ae. albopictus were found in all seven health districts of the country with high abundance of Ae. aegypti in the most urbanised district, Agua Grande. Both Aedes species bred mainly in used tyres, discarded tanks and water storage containers. In both survey periods, the Breteau (BI > 50), house (HI > 35%) and container (CI > 20%) indices were higher than the thresholds established by WHO to indicate high potential risk of dengue transmission. The Ae. aegypti sampled were susceptible to all insecticides tested except dichlorodiphenyltrichloroethane (DDT) (9.2% mortality, resistant), bendiocarb (61.4% mortality, resistant) and alpha-cypermethrin (97% mortality, probable resistant). A full recovery was observed in Ae. aegypti resistant to bendiocarb after pre-exposure to synergist PBO. Only one Ae. aegypti specimen was found carrying F1534C mutation. CONCLUSIONS/SIGNIFICANCE: These findings revealed a high potential risk for dengue transmission throughout the year, with the bulk of larval breeding occurring in used tyres, water storage and discarded containers. Most of the insecticides tested remain effective to control Aedes vectors in Sao Tome, except DDT and bendiocarb. These data underline the importance of raising community awareness and implementing routine dengue vector control strategies to prevent further outbreaks in Sao Tome and Principe, and elsewhere in the subregion.

Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda.

BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial. METHODS: A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 - 40) with substantial between-cluster variation, ranging from 1% to 55%. CONCLUSION: In this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets.

An absence of evidence breeds contempt: A qualitative study of health system stakeholder perceptions of the quality of medicines available in Senegal.

Poor-quality medicines pose a significant challenge for health systems in low- to middle-income countries (LMICs),with recent deaths in multiple countries following ingestion of substandard cough syrups emphasising the need for quality-assurance of medicines in our increasingly interconnected global markets. Research also suggests that the source (country of manufacture) and type of medicine (generic/brand) are perceived to be associated with medicine quality. This study explores perceptions of medicines quality among national stakeholders of a medicines quality assurance system (MQAS) in sub-Saharan Africa. Through semi-structured interviews (n = 29) with managers from organisations responsible for the MQAS, public-sector doctors and nurses, and regulated private-sector pharmacists in three urban centres in Senegal in 2013. A thematic approach to analysis was undertaken with themes organised under three main categories, the source of drugs, the type of medicine, and medicines storage. A key emerging theme was the perception of the inferior quality of generic medicines, especially those produced in Asia and Africa, as they were lower in cost and thus believed to be less effective in alleviating symptoms than their brand versions. Medicines in Senegal's less regulated (informal) street markets were also thought to be of poor-quality as they were not subjected to national regulatory processes or stored appropriately, resulting in exposure to direct sunlight and high temperatures. In contrast, the interviewees expressed confidence in medicines quality within the regulated sectors (public and private retail pharmacies) attributed to stringent national medicines regulation, secure medicines supply chains and adequate technical capacity to survey and analyse for medicines quality. Also, the views expressed typically described a medicine's quality in terms of its effectiveness in alleviating the symptoms of ill health (efficacy of a medicine).These perceptions may have implications for developing national medicines policy, the procurement and supply of affordable medicines and consumers' decision-making when purchasing medicines. Indeed, a proclivity for supplying and purchasing more expensive brand medicines may act as a barrier to accessing essential medicines.

Is it possible for drug shops to abide by the formal rules? The structural determinants of community medicine sales in Uganda.

The medicines retail sector is an essential element of many health systems in Africa and Asia, but it is also well known for poor practice. In the literature, it is recognised that improvements in the sector can only be made if more effective forms of governance and regulation can be identified. Recent debate suggests that interventions responsive to structural constraints that shape and underpin poor practice is a useful way forward. This paper presents data from a mixed-methods study conducted to explore regulation and the professional, economic and social constraints that shape rule breaking among drug shops in one district in Uganda. Our findings show that regulatory systems are undermined by frequent informal payments, and that although drug shops are often run by qualified staff, many are unlicensed and sell medicines beyond their legal permits. Most shops have either a small profit or a loss and rely on family and friends for additional resources as they compete in a highly saturated market. We argue that in the current context, drug shop vendors are survivalist entrepreneurs operating in a market in which it is extremely difficult to abide by policy, remain profitable and provide a service to the community. Structural changes in the medicines market, including removing unqualified sellers and making adjustments to policy are likely prerequisite if drug shops are to become places where individuals can earn a living, abide by the rules and facilitate access to medicines for people living in some of the world's poorest countries.

Regulations on the Use of Antibiotics in Livestock Production in South America: A Comparative Literature Analysis.

As a global health problem, antimicrobial resistance (AMR) crosses national borders, leading UN (United Nations) multilateral agencies to call for all countries to improve the stewardship of antibiotics in humans and animals. South American countries have changed their regulations regarding antibiotic use in livestock production. This literature review examines how far the five largest meat-producing countries in South America (Argentina, Brazil, Chile, Colombia, and Uruguay) have come in terms of the relevant legislation. Rules on market entry (marketing authorization and official distribution systems) are already set in all countries examined. Four countries do not allow growth promoters based on critically important antibiotics, and countries have also begun to set guidelines and minimum welfare and biosecurity requirements to reduce the therapeutic demand for antibiotics. Nonetheless, there are aspects related to the distribution, use, and disposal of antibiotics that need to be developed further. In conclusion, legislation in South American countries is moving towards the goals set by UN multilateral agencies, but more can be done. Differences between countries' rules and the gold standards set by the World Organization for Animal Health (OIE), World Health Organization (WHO), and Food and Agriculture Organization of the United Nations (FAO) reveal possible adaptations to the countries' realities. Further studies must examine compliance with the legislation already set and investigate other tools that can be used alongside legislation as a driving force to change stakeholder behaviour.