Household sampling through geocoded points and satellite view: A step-by-step approach to implement a spatial sampling method for demographic and health surveys in areas without population sampling frame and with limited resource settings.

INTRODUCTION: Spatial sampling is increasingly used in health surveys as it provides a simple way to randomly select target populations on sites where reliable and complete data on the general population are not available. However, the previously implemented protocols have been poorly detailed, making replication difficult or even impossible. To our knowledge, ours is the first document describing step-by-step an efficient spatial sampling method for health surveys. Our objective is to facilitate the rapid acquisition of the technical skills and know-how necessary for its deployment. METHODS: The spatial sampling design is based on the random generation of geocoded points in the study area. Afterwards, these points were projected on the satellite view of Google Earth Pro™ software and the identified buildings were selected for field visits. A detailed formula of the number of points required, considering non-responses, is proposed. Density of buildings was determined by drawing circles around points and by using a replacement strategy when interviewing was unachievable. The method was implemented for a cross-sectional study during the April-May 2016 period in Cotonou (Bénin). The accuracy of the collected data was assessed by comparing them to those of the Cotonou national census. RESULT: This approach does not require prior displacement in the study area and only 1% of identified buildings with Google Earth Pro™ were no longer extant. Most of the measurements resulting from the general census were within the confidence intervals of those calculated with the sample data. Furthermore, the range of measurements resulting from the general census was similar to those calculated with the sample data. These include, for example, the proportion of the foreign population (unweighted 8.9%/weighted 9% versus 8.5% in census data), the proportion of adults over 17 years of age (56.7% versus 57% in census data), the proportion of households whose head is not educated (unweighted 21.9%/weighted 22.8% versus 21.1% in census data). CONCLUSION: This article illustrates how an epidemiological field survey based on spatial sampling can be successfully implemented at low cost, quickly and with little technical and theoretical knowledge. While statistically similar to simple random sampling, this survey method greatly simplifies its implementation.

Low use of artemisinin-based combination therapy for febrile children under five and barriers to correct fever management in Benin: a decade after WHO recommendation.

BACKGROUND: Artemisinin-based combination therapy (ACT), used to treat uncomplicated malaria cases, is one of the main strategies of malaria control and elimination. One of the main objectives of the Benin National Malaria Control Program's (NMCP) strategic plan is to ensure that at least 80% of uncomplicated malaria is treated with ACT within 24 h. Therefore, it was of great interest to measure whether the country case management of fever amongst children under five, adhered to the NMCP's strategic plan and look into the barriers to the use of ACT. METHODS: A cross-sectional survey based on a cluster and multi-stage sampling was conducted in two rural health districts in Benin. We recruited 768 and 594 children under five years were included in the northern and in the southern respectively. Data was collected on the general use of ACT and on the correct use of ACT that adheres to the NMCP's strategy, as well as the barriers that prevent the proper management of fever amongst children. To assess the certain predictors of ACT usage, logistic regression was used, while taking into account the cluster random effect. RESULTS: Among febrile children aged 6 to 59 months, 20.7% in the south and 33.9% in north received ACT. The correct use of ACT, was very low, 5.8% and in southern and 8.6% northern areas. Caregivers who received information on ACT were 3.13 time more likely in the south and 2.98 time more likely in the north to give ACT to their feverish child, PPR = 3.13[1.72-4.15] and PPR = 2.98 [2.72-3.11] respectively. Chloroquine and quinine, other malaria treatments not recommended by NMCP, were still being used in both areas: 12.3 and 3.3% in the south and 11.4 and 3.0% in the north. CONCLUSION: In Benin, the use and the correct use of ACT for febrile children remains low. The study also showed that having received information about the use of ACT is positively associated with the use of ACT. This point highlights the fact that efforts may not have been sufficiently integrated with social communication, which should be based on the behavioural determinants of populations.

Child age or weight: difficulties related to the prescription of the right dosage of antimalarial combinations to treat children in Senegal.

Less than a year after the introduction of amodiaquine (AQ)/sulfadoxine-pyrimethamine (SP) as the first-line antimalarial treatment in Senegal, our study aimed to assess patients' drug intake and check its correspondence with nurses' prescription-adherence, the national guidelines regimen and theoretical dosage. The study was conducted at five health centers. Children aged 2-10 years who were prescribed AQ/SP by the nurse were recruited. At day 3, caregivers were questioned about treatment adherence. We collected information about nurses' prescriptions and conducted in-depth interviews on prescription patterns. Among the 289 children who were recruited, 35.3% took less than 80% of the prescribed doses. Nevertheless, 47.7% and 83.7% respectively for AQ and SP received a dosage higher than the theoretical dosage. Age-weight discrepancy leads to overprescribing drugs: nurses acknowledged using the child's age more often than weight to determine the dosage if the child has a low weight. Under and overdosing are not only due to patient practices but causes related to national guidelines and health staff practices. For successful implementation and utilization of antimalarial combinations in Africa, countries should really focus on nurses' training. National guidelines should also be based on national average weight instead of international tables.

[Knowledge and practice among health workers from the Thiès region with regard to new malaria treatment policies]. / Connaissances et pratiques des agents de santé de la région de Thiès concernant la nouvelle thérapie des accès palustres.

The emergence of increasing plasmodium falciparum resistance to chloroquine in Africa has prompted national malaria programmes to develop new policies regarding appropriate and essential treatment, moving from the use of chloroquine to a new set of bi-therapy methods. In Senegal, the malaria treatment policy has shifted from chloroquine to amodiaquine/sulfadoxine-pyrimethamine. The authors studied the availability of these new drugs and their use by the care providers in 10 rural health district dispensaries. Patient records were examined and nurses were interviewed on their knowledge about and implementation of the new policy. It was noted that the nurses have not yet mastered the proper use of these new medications, and the prescriptions given were not always in line with regulations and practice corresponding to the required or necessary doses. The families which were interviewed stated that they were not aware of the changes in treatment which had been recommended. The conclusion of this study was that it brought to the forefront the need to put specific emphasis on population information and awareness campaigns as well as that of ensuring that caregivers receive thorough training to secure the successful and sustainable implementation and maintenance of the new policy.

[Placental malaria and pregnancy outcome in a peri urban area in Senegal]. / Infection palustre placentaire et issue de l'accouchement dans une zone péri-urbaine au Sénégal.

BACKGROUND: In areas of seasonal malaria transmission in Senegal, two previous studies have found that maternal direct obstetrics deaths and preeclampsia were more frequent during the rainy/malaria season. These observations suggest a possible link between malaria and maternal or fetal morbidity and mortality. In this study, we explore this link in a peri urban maternity in Senegal. METHODS: We carried out an exhaustive survey at "Maternité Roi-Baudouin" in Guédiawaye, which is the main maternity of the suburb of Dakar, Senegal. From August 1998 to December 1999, we included all women attending the maternity for delivery. Placental malaria was diagnosed by the presence of parasites or malarial pigment in placental apposition. Delivery diagnosis was assessed by obstetricians or midwives. Sociodemographic data and information about chloroquine intake were recorded. Multivariate analysis was performed to compare prevalence of placental malaria between normal and poor deliveries outcomes. RESULTS: Eight thousand two hundred and seventy three women were included. There were 5597 (67.7%) normal deliveries, 1214 (14.6%) low birth weight babies (<2500 g) and 1462 (17.7%) deliveries with a maternal or fetal poor outcome. Placental malaria prevalence was 9.5% (785/8273). Placental malaria was associated with low birth weight (adjusted OR=2.06 (1.72-2.57)), preterm birth (adjusted OR=3.51 (1.84-6.68)) and perinatal mortality (adjusted OR=2.56 (1.65-3.97)). We did not find an association between placental malaria and occurrence of a maternal pathology (dystocia, preeclampsia, eclampsia, retroplacental haematoma). CONCLUSION: Although malaria at delivery is not associated with occurrence of a maternal obstetric pathology, it has detrimental effects for the fetus and newborns. Effective antimalarial strategies during the antenatal period are urgently needed.

Low malaria morbidity in a cohort of Senegalese children with free access to health structures.

We report the impact of the free access to health facilities on malaria morbidity in children from two to 15 years old, during a malaria transmission season in Niakhar, Senegal. Between July and December 2002, 227 malaria attacks occured in 566 children. Only one case of severe malaria was observed and no death has been reported. Our results demonstrate furthermore that easier access to health facilities and to early treatment is playing a key role in malaria control.

Dynamics of anti-VAR2CSA immunoglobulin G response in a cohort of senegalese pregnant women.

BACKGROUND: Pregnancy-associated malaria (PAM) is precipitated by the accumulation of parasites in the placental intervillous spaces and causes maternal anemia and low birth weight. In PAM, placental parasites adhere to chondroitin sulfate A (CSA) through a unique set of variant surface antigens (VSAPAM). Several studies have shown that 1 var gene, var2csa, is transcribed at high levels and expressed in CSA-binding Plasmodium falciparum parasites. METHODS: Plasma levels of anti-VAR2CSA immunoglobulin G (IgG) in Senegalese women were measured during pregnancy by enzyme-linked immunosorbent assay, using 3 recombinant proteins representing 3 domains of the var2csa gene product. RESULTS: The 3 recombinant proteins were specifically recognized by plasma from pregnant women but not by control plasma. A parity-dependent recognition pattern was observed with 2 of the 3 VAR2CSA antigens. A kinetic study demonstrated that a single P. falciparum infection was able to trigger a VAR2CSA-specific antibody response. Among women with infected placentas, women with high anti-VAR2CSA IgG levels at enrollment were more likely to present with a past infection than with an acute/chronic infection. CONCLUSIONS: Anti-VAR2CSA IgGs are involved in clinical protection against pregnancy-associated malaria and strengthens the hope for making a VAR2CSA-based vaccine.

[Outcomes of improved care on health center activity in a rural area of Senegal]. / Effets de l'amélioration de l'offre de soins sur l'activité d'un poste de santé en zone rurale au Sénégal.

BACKGROUND: This study aimed at analyzing the short-term effects of an improvement in care offer on dispensary activity in a rural area of Senegal. METHODS: The Niakhar health center, situated 150 km east of Dakar, underwent significant changes during the years 1998 and 1999: a hospital unit was built, the maternity ward was extended and the patient reception facilities were refurbished and reorganized. We examined dispensary registers before (1997) and after (2000) this period of time. We focused on data reporting activity and utilization of the health center. We also studied the users'perception of these improvements. Interviews were conducted with 39 families to measure the consequences of this change on their attitudes towards treatment. RESULTS: The number of consultants increased by 49.8% from 1997 to 2000. Activity peaked during the rainy season, during which consultations were twice as numerous in 2000 as in 1997. However a similar increase was noticed in another health center close to Niakhar and could be attributed to the high precipitation rate observed in this area in the year 2000. For children, there was no difference in center utilization between the two study years as each child went to the dispensary 1.18 and 1.21 times a year in 1997 and 2000 respectively. The maternity activity exhibited a 68% increase in deliveries. Families interviewed said the dispensary was significantly improved, but they were not able to change their practice, due to lack of financial resources and poor drug supply. CONCLUSION: The changes in care offer did not seem to have yielded the expected effect on care activity. The appointment of a midwife as well as improvements in both technical facilities and awareness contributed to the increase in maternity use.

Less HLA-G expression in Plasmodium falciparum-infected third trimester placentas is associated with more natural killer cells.

During pregnancy, maternal immune tolerance of the fetal semi-allogeneic graft is partly the consequence of extravillous trophoblast HLA-G expression and its interaction with natural killer (NK) cells. Plasmodium falciparum malaria is frequently associated with maternal and fetal complications. Local HLA-G expression and the number of NK cells were evaluated immunohistochemically in P. falciparum-infected and uninfected placentas (15 each) collected in a seasonal malaria-hypoendemic area. In control placentas, HLA-G was almost always expressed in extravillous trophoblast whereas, in infected placentas, it was significantly more weakly expressed in extravillous trophoblast but was also detected in intervillous space macrophages. NK cells were evaluated in intervillous and intravillous spaces and in basal plate. NK cells were always more abundant in basal plate than in intervillous and intravillous spaces in infected or control placentas. For each area, more NK cells were seen in infected than control placentas. These data suggest that HLA-G down-regulation and more NK cells in placentas may be among the mechanisms involved in poor birth outcome associated with P. falciparum infection.

[Placental infection by Plasmodium falciparum in an urban area of Senegal]. / Infection du placenta par Plasmodium falciparum en zone urbaine au Sénégal.

OBJECTIVES: This study aimed at describing the burden of malaria at delivery in a urban maternity in Senegal. We measured the prevalence of placental malaria infection. We described the association between placental malaria and low birth weight and the impact of chemoprophylaxis. STUDY AREA: Guediawaye is the most important suburb of the city of Dakar, Senegal, surrounded by a permanent marsh (niayes). Malaria in this area is hypo endemic transmission: 1 infective bite/person/year. An. arabiensis is the principal vector and P. falciparum (98%) the most frequent species. The Maternité Roi Baudoin in Guediawaye is the gynecologic and obstetrical reference centre of this area with more than 6000 deliveries/year. METHODS: We carried out an exhaustive survey from August 98 to December 99 at the maternité Roi Baudoin in Guediawaye. The socio-demographic data, the clinical data and information about prophylaxy were collected by questionnary. For each woman at delivery, one placental apposition was carried out. Presence of trophozoïtes or schizontes indicated malaria placental infection. RESULTS: 8310 women were included in the study. They were from 13 to 49 years old with an average age of 26.1; 28% were primigravidae. The prevalence of placental malaria infection was 8.1% (674/8310) [Ic95: 7.4-8.8%]. Schizontes were present in 80.5% of infected placenta. The prevalence was 8.8% within primigravidae group and 7.4% in the other parity groups, p = 0.28 (NS). Placental infection was present all the year long. However, there were important seasonal variations. The risk of placental infection increased during seasonal transmission (> 10%) compared to the period of low transmission (3%). The prevalence of placental malaria was lower in the group of women who declares regular chloroquine intake compared with those who declared taking no prophylaxy or irregular prophylaxy (RR = 0.78 [0.62-0.98]). The risk of low birth weight was of 1.9 [1.6-2.1] when the placenta was infected compared with non infected placenta. CONCLUSION: This study indicates that placental malaria infection is frequent in this low transmission area where more than 70% of women declared taking regular chloroquine. This observation could be explained by a resistance of P. falciparum to chloroquine or a poor observance of chemoprophylaxis.

[Limits and weaknesses of intermittent treatment in malaria prevention]. / Limites et faiblesses du traitement intermittent dans la prévention du paludisme.

WHO proposal of a new strategy for the control of malaria, intermittent treatment using sulfadoxine-pyrimethamine, encounters various conceptual and logistic problems. First, the treatment is dedicated only to a very small part of the population which is not representative of the population at risk. Secondly, it largely underestimates the risks of this type of drugs. At last, the difficulties of its management should lead to hamper this strategy. It would be preferable to study the real causes of the current strategy failure and to take it into account for a new strategy.

[The particularities of malaria in the child]. / Les particularités du paludisme chez l'enfant.

Malaria is generally recognized as the main cause of infant mortality and/or morbidity in tropical regions of Africa. However the exact impact of the disease is still difficult to evaluate due to the lack of adequate facilities for data collection and screening. Another major unsolved problem involves diagnosis of malaria attacks in infants. Due to repeated exposure to the parasite and progressive development of immunity to malaria, a child's susceptibility changes with age. In addition the clinical, parasitological and immunological form of the disease varies from one child to another depending on his or her risk and protection factors as well as genetic, physiological and environmental factors. Because of these special features, diagnosis of malaria is complicated not only in the neonatal period but also throughout infancy. A better understanding of these features, which determine the expression of the disease in infants, will be required to optimize management of malarial attacks and improve preventive measures implemented in Africa to lower malaria-related morbidity and mortality.

Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine.

Plasmodium falciparum gametocytemia and its related infectivity for mosquitoes was studied in 115 patients (median age = 18 years, range = 4-45) with simple malaria attacks who lived in the hypoendemic area of Dakar, Senegal. Patients were included in a 28-day in vivo sensitivity test after treatment with chloroquine (CQ, n = 82) or sulfadoxine plus pyrimethamine (SP, n = 33). The prevalence of resistant infections was 58.5% in those treated with CQ and 0% in those treated with SP. The gametocytemia peaked at day 7 after treatment. The maximal gametocyte prevalence was 38.2% in the CQ-sensitive infection group, 89.6% in the CQ-resistant group, and 97.0% in those treated with SP The maximal geometric mean gametocytemia was 2.19/microl in the CQ-sensitive infection group, 29.12/microl in the CQ-resistant group and 85.55/microl in those treated with SP. The period between appearance of the first clinical symptom and treatment was positively related to gametocyte prevalence at days 0 and 2. Experimental infection of wild Anopheles arabiensis using membrane feeders was performed at days 0 and 7, and mosquito infectivity was measured by oocyst detection on the midgut. At day 0, 14.1% of the patients had infected at least 1 mosquito, and at day 7, this value was 38.5%. The mean percentage of infected mosquitoes was 3.2% at day 0 and 12.6% at day 7. At day 7 after treatment with CQ, the relative risk for patients with resistant infections of infecting anophelines was 4.07 higher than in those with sensitive infections. No difference was observed in infectivity for mosquitoes between RI-type resistance and the RII + RIII-type resistance. A sporonticidal effect of SP was observed at day 7 after treatment. These data show that P. falciparum gametocytes and their infectivity for mosquitoes were differentiated according to the drug used, its efficacy, and the duration of symptoms before treatment; they were not dependent on the density of asexual stages. Prompt treatment of malaria cases performed at the beginning of symptoms could limit the spread of resistant parasites.

Longitudinal study of Plasmodium falciparum infection and immune responses in infants with or without the sickle cell trait.

BACKGROUND: Individuals may be homozygous (SS) or heterozygous (AS) sickle cell gene carriers or have normal adult haemoglobin (AA). Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known. METHODS: We followed two cohorts of children. The first was enrolled at birth (156 newborn babies) and the second at 24-36 months old (84 children). Both cohorts were followed for 30 months; monthly for parasitological data and half yearly for immunological data. RESULTS: In the first cohort, 22%, and in the second 13% of children were AS. Whatever their age parasite prevalence rates were similar in AA and AS individuals. Mean parasite densities increased less rapidly with age in AS than in AA children, and were significantly lower in AS than in AA children >48 months old. The AA children tended to be more often admitted to hospital than AS children (22% versus 11%, NS). Both anti-Plasmodium falciparum and anti-Pfl55/RESA antibody rates increased more rapidly in AA than in AS children. Conversely, the prevalence rate of cellular responders to the Pfl55/RESA antigen was similar in AA and AS children during the first 2 years of life, then it was higher in AS than in AA children. CONCLUSIONS: Sickle cell trait related antimalarial protection varies with age. The role of the modifications of the specific immune response to P. falciparum in explaining the protection of AS children against malaria is discussed.

Stochastic algorithms for Markov models estimation with intermittent missing data.

Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed.

[The microwave oven for drying thick blood smears. Benefits and limits for microscopic observation of Plasmodium falciparum trophozoites and gametocytes]. / Le four à micro-ondes pour le séchage des gouttes épaisses. Intérêt et limites dans l'observation microscopique des trophozoïtes et des gamétocytes de Plasmodium falciparum.

The micro-wave oven permits a rapid drying of thick blood smears classically used for parasitological malaria diagnosis. In order to evaluate this type of drying on the microscopic reading, a study was carried out in an hyperendemic area of malaria with 382 asymptomatic volunteers of all ages. Two thick smears were made for each volunteer, one immediately dried with a micro-wave oven for one minute, the second dried in the open air without any intervention. A single microscopist examined all the thick smears. The observation of Plasmodium falciparum trophozoites differed significantly between the two methods, the prevalence was 50% by normal drying versus 41% by the micro-wave oven. The geometric mean of the trophozoite number for positive thick smears was significantly lower with the micro-wave oven. When the parasitological density with normal drying was lower than 200 trophozoites/microliter of blood, 54% of results were wrongly negative with the micro-wave oven. On the other hand, the observation of P. falciparum gametocytes was significantly facilitated after drying with the micro-wave oven; the prevalence was 8% with normal drying versus 12% by micro-wave oven. In conclusion, the use of the micro-wave oven for the drying of thick smears is not recommended for malaria diagnosis although it improves the observation and counting of P. falciparum gametocytes.

Effect of chloroquine prophylaxis during pregnancy on maternal haematocrit.

Two controlled trials of chloroquine prophylaxis during pregnancy were performed, one in Burkina Faso in 1987, on all pregnant women, and the other in Cameroon in 1992, on primigravidae only. Maternal haematocrit at delivery was found to be significantly higher in those women who had received chloroquine than in those who had not, both in Burkina Faso (37.4% v. 36.5%; P = 0.01) and in Cameroon (34.8% v. 32.8%; P = 0.02). Anaemia, defined as an haematocrit of < 30%, was also less common in those treated with chloroquine (6.3% v. 8.5% in Burkina Faso and 8.3% v. 18.4% in Cameroon) but this difference was not significant in either country. A slight improvement in haematological status when prophylaxis is given has also been observed in similar studies performed in other tropical countries. The present results confirm the usefulness of targeting antimalarial prophylaxis at pregnant women. Such prophylaxis during the first pregnancy also increases birthweight.

Prevalence of and risk factors for anemia in young children in southern Cameroon.

Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.