Asymptomatic Plasmodium falciparum carriage and clinical disease: a 5-year community-based longitudinal study in The Gambia.

BACKGROUND: Carriers of persistent asymptomatic Plasmodium falciparum infections constitute an infectious reservoir that maintains malaria transmission. Understanding the extent of carriage and characteristics of carriers specific to endemic areas could guide use of interventions to reduce infectious reservoir. METHODS: In eastern Gambia, an all-age cohort from four villages was followed up from 2012 to 2016. Each year, cross-sectional surveys were conducted at the end of the malaria transmission season (January) and just before the start of the next one (June) to determine asymptomatic P. falciparum carriage. Passive case detection was conducted during each transmission season (August to January) to determine incidence of clinical malaria. Association between carriage at the end of the season and at start of the next one and the risk factors for this were assessed. Effect of carriage before start of the season on risk of clinical malaria during the season was also examined. RESULTS: A total of 1403 individuals-1154 from a semi-urban village and 249 from three rural villages were enrolled; median age was 12 years (interquartile range [IQR] 6, 30) and 12 years (IQR 7, 27) respectively. In adjusted analysis, asymptomatic P. falciparum carriage at the end of a transmission season and carriage just before start of the next one were strongly associated (adjusted odds ratio [aOR] = 19.99; 95% CI 12.57-31.77, p < 0.001). The odds of persistent carriage (i.e. infected both in January and in June) were higher in rural villages (aOR = 13.0; 95% CI 6.33-26.88, p < 0.001) and in children aged 5-15 years (aOR = 5.03; 95% CI 2.47-10.23, p = < 0.001). In the rural villages, carriage before start of the season was associated with a lower risk of clinical malaria during the season (incidence risk ratio [IRR] 0.48, 95% CI 0.27-0.81, p = 0.007). CONCLUSIONS: Asymptomatic P. falciparum carriage at the end of a transmission season strongly predicted carriage just before start of the next one. Interventions that clear persistent asymptomatic infections when targeted at the subpopulation with high risk of carriage may reduce the infectious reservoir responsible for launching seasonal transmission.

Clustering of asymptomatic Plasmodium falciparum infection and the effectiveness of targeted malaria control measures.

BACKGROUND: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. METHODS: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. RESULTS: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. CONCLUSIONS: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.

Non-falciparum malaria infections in pregnant women in West Africa.

BACKGROUND: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. CONCLUSIONS: Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites.

Seasonal variation in haematological and biochemical reference values for healthy young children in The Gambia.

BACKGROUND: Haematological and biochemistry reference values for children are important for interpreting clinical and research results however, differences in demography and environment poses a challenge when comparing results. The study defines reference intervals for haematological and biochemistry parameters and examines the effect of seasonality in malaria transmission. METHODS: Blood samples collected from clinically healthy children, aged 12-59 months, in two surveys during the dry and wet season in the Upper River region of The Gambia were processed and the data analysed to generate reference intervals based on the 2.5(th) and 97.5(th) percentiles of the data. RESULTS: Analysis was based on data from 1141 children with median age of 32 months. The mean values for the total white cell count and differentials; lymphocyte, monocyte and neutrophil decreased with increasing age, were lower in males and higher in the wet season survey. However, platelet values declined with age (p < 0.0001). There was no evidence of effect of gender on mean values of AST, ALT, lymphocytes, monocytes, platelets and haemoglobin. CONCLUSION: Mean estimates for haematological and biochemistry reference intervals are affected by age and seasonality in the first five years of life. This consistency is important for harmonisation of reference values for clinical care and interpretation of trial results.

Correction: Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0244109.].

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.

BACKGROUND: Preterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. AIM: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. METHODS: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. RESULTS: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). CONCLUSION: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.

Marked variability in institutional deliveries and neonatal outcomes during the COVID-19 lockdown in Nigeria.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and the interventions to mitigate its spread impacted access to healthcare, including hospital births and newborn care. This study evaluated the impact of COVID-19 lockdown measures on newborn service utilization in Nigeria. METHODS: The records of women who delivered in hospitals and babies admitted to neonatal wards were retrospectively reviewed before (March 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic lockdown in selected facilities in Nigeria. RESULTS: There was a nationwide reduction in institutional deliveries during the COVID-19 lockdown period in Nigeria, with 14 444 before and 11 723 during the lockdown-a decrease of 18.8%. The number of preterm admissions decreased during the lockdown period (30.6% during lockdown vs 32.6% pre-lockdown), but the percentage of outborn preterm admissions remained unchanged. Newborn admissions varied between zones with no consistent pattern. Although neonatal jaundice and prematurity remained the most common reasons for admission, severe perinatal asphyxia increased by nearly 50%. Neonatal mortality was significantly higher during the COVID-19 lockdown compared with pre-lockdown (110.6/1000 [11.1%] vs 91.4/1000 [9.1%], respectively; p=0.01). The odds of a newborn dying were about four times higher if delivered outside the facility during the lockdown (p<0.001). CONCLUSIONS: The COVID-19 lockdown had markedly deleterious effects on healthcare seeking for deliveries and neonatal care that varied between zones with no consistent pattern.

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya.

OBJECTIVES: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. DESIGN: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. SETTING: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. PARTICIPANTS: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. RESULTS: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. CONCLUSION: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants.

Enteral Feeding Practices for Very Preterm and Very Low Birth Weight Infants in Nigeria and Kenya.

Background: Optimizing nutrition in very preterm (28-32 weeks gestation) and very low birth weight (VLBW; 1,000 g to <1,500 g) infants has potential to improve their survival, growth, and long-term health outcomes. Aim: To assess feeding practices in Nigeria and Kenya for very preterm and VLBW newborn infants. Methods: This was a cross-sectional study where convenience sampling was used. A standard questionnaire was sent to doctors working in neonatal units in Nigeria and Kenya. Results: Of 50 respondents, 37 (74.0%) were from Nigeria and 13 (26.0%) from Kenya. All initiated enteral feeds with breastmilk, with 24 (48.0%) initiating within 24 h. Only 28 (56.0%) used written feeding guidelines. Starting volumes ranged between 10 and 80 ml/kg/day. Median volume advancement of feeds was 20 ml/kg/day (IQR 10-20) with infants reaching full feeds in 8 days (IQR 6-12). 26 (52.0%) of the units fed the infants 2 hourly. Breastmilk fortification was practiced in 7 (14.0%) units, while folate, iron, calcium, and phosphorus were prescribed in 42 (84.0%), 36 (72.0%), 22 (44.0%), 5 (10.0%) of these units, respectively. No unit had access to donor breastmilk, and only 18 (36.0%) had storage facilities for expressed breastmilk. Twelve (24.0%) used wet nurses whilst 30 (60.0%) used formula feeds. Conclusion: Feeding practices for very preterm and VLBW infants vary widely within Nigeria and Kenya, likely because of lack of locally generated evidence. High quality research that informs the feeding of these infants in the context of limited human resources, technology, and consumables, is urgently needed.

Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

OBJECTIVE: To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. STUDY DESIGN: In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. RESULTS: 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73-28.39), VLBW (6.92; 4.06-11.79), congenital anomaly (4.93; 2.42-10.05), abdominal condition (2.86; 1.40-5.83), birth asphyxia (2.44; 1.52-3.92), respiratory condition (1.46; 1.08-2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28-2.85). Mortality was reduced if mothers received a partial (0.51; 0.28-0.93) or full treatment course (0.44; 0.21-0.92) of dexamethasone before preterm delivery. CONCLUSION: Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn.

Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis.

BACKGROUND: Malaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes. METHODS: We undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999-December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001-December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions. FINDINGS: From 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000-04 to 97 g/L in 2005-07), and mean age of paediatric malaria admissions increased from 3.9 years (95% CI 3.7-4.0) to 5.6 years (5.0-6.2). INTERPRETATION: A large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance.

Development of a data collection and management system in West Africa: challenges and sustainability.

BACKGROUND: Developing and sustaining a data collection and management system (DCMS) is difficult in malaria-endemic countries because of limitations in internet bandwidth, computer resources and numbers of trained personnel. The premise of this paper is that development of a DCMS in West Africa was a critically important outcome of the West African International Centers of Excellence for Malaria Research. The purposes of this paper are to make that information available to other investigators and to encourage the linkage of DCMSs to international research and Ministry of Health data systems and repositories. METHODS: We designed and implemented a DCMS to link study sites in Mali, Senegal and The Gambia. This system was based on case report forms for epidemiologic, entomologic, clinical and laboratory aspects of plasmodial infection and malarial disease for a longitudinal cohort study and included on-site training for Principal Investigators and Data Managers. Based on this experience, we propose guidelines for the design and sustainability of DCMSs in environments with limited resources and personnel. RESULTS: From 2012 to 2017, we performed biannual thick smear surveys for plasmodial infection, mosquito collections for anopheline biting rates and sporozoite rates and year-round passive case detection for malarial disease in four longitudinal cohorts with 7708 individuals and 918 households in Senegal, The Gambia and Mali. Major challenges included the development of uniform definitions and reporting, assessment of data entry error rates, unstable and limited internet access and software and technology maintenance. Strengths included entomologic collections linked to longitudinal cohort studies, on-site data centres and a cloud-based data repository. CONCLUSIONS: At a time when research on diseases of poverty in low and middle-income countries is a global priority, the resources available to ensure accurate data collection and the electronic availability of those data remain severely limited. Based on our experience, we suggest the development of a regional DCMS. This approach is more economical than separate data centres and has the potential to improve data quality by encouraging shared case definitions, data validation strategies and analytic approaches including the molecular analysis of treatment successes and failures.

A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy.

BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. METHODS AND FINDINGS: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. CONCLUSIONS: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122.

Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia.

BACKGROUND: Severe malaria (SM) is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management. METHODS: A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae. FINDINGS: Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7-7.3]), respiratory distress (OR 2.4 [95%CI, 1.7-3.2]), hypoglycemia (OR 1.7 [95%CI, 1.2-2.3]), jaundice (OR 1.9 [95%CI, 1.2-2.9]) and renal failure (OR 11.1 [95%CI, 3.3-36.5]) were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60-0.65]) and impaired consciousness (AUC 0.61[95%CI, 0.59-0.63]), which were comparable to the ability of hyperlactatemia (blood lactate>5 mM) to predict death (AUC 0.64 [95%CI, 0.55-0.72]). A Blantyre coma score (BCS) of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68-0.72]), and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67-0.76]).The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71-0.76]). CONCLUSION: The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM.

Sahel, savana, riverine and urban malaria in West Africa: Similar control policies with different outcomes.

The study sites for the West African ICEMR are in three countries (The Gambia, Senegal, Mali) and are located within 750 km of each other. In addition, the National Malaria Control Programmes of these countries have virtually identical policies: (1) Artemisinin Combination Therapies (ACTs) for the treatment of symptomatic Plasmodium falciparum infection, (2) Long-Lasting Insecticide-treated bed Nets (LLINs) to reduce the Entomololgic Inoculation Rate (EIR), and (3) sulfadoxine-pyrimethamine for the Intermittent Preventive Treatment of malaria during pregnancy (IPTp). However, the prevalence of P. falciparum malaria and the status of malaria control vary markedly across the four sites with differences in the duration of the transmission season (from 4-5 to 10-11 months), the intensity of transmission (with EIRs from unmeasurably low to 4-5 per person per month), multiplicity of infection (from a mean of 1.0 to means of 2-5) and the status of malaria control (from areas which have virtually no control to areas that are at the threshold of malaria elimination). The most important priority is the need to obtain comparable data on the population-based prevalence, incidence and transmission of malaria before new candidate interventions or combinations of interventions are introduced for malaria control.

Improving malaria control in West Africa: interruption of transmission as a paradigm shift.

With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases.