[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area]. / Dépistage néonatal ciblé de la drépanocytose : limites du test de falciformation (test d'Emmel) dans le bilan prénatal en zone ouest africaine.

BACKGROUND: Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. METHODS: From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. RESULTS: Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. CONCLUSION: Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist.

[Radiochemotherapy for the treatment ofmuscle invasive bladder tumors in a west african radiotherapy service]. / Radiochimiotherapie pour le traitement des tumeurs de vessie infiltrant lemuscle dans un service de radiotherapie ouest africaine.

OBJECTIF: The aim of this study was to describe the results of radiochemotherapy in patients after transurethral resection of muscle invasive bladder tumors. MATERIAL AND METHODS: A retrospective study from May 2014 to May 2016 in the radiotherapy department of the Mali Hospital. Have been included, all patients with bladder cancer infiltrating the muscle. Secondary cancers of the bladder and metastatic forms have been excluded from our study. Transurethral resection of bladder was performed. Neoadjuvant chemotherapy with paclitaxel- carboplatin was administered every three weeks in all patients, then external phototherapy 6 MV at a dose of 66 Gy due to 2 Gy of 5 sessions per week 6MV photon of external beam radiotherapy at a dose of 66 Gy due to 2 Gy of 5 sessions per week associated with concomitant cisplatin at dose of 40mg / m2 / week. RESULTS: Eight patients were included in ourstudy. The average age of 53.75 ± 14.84 years. The male sex was predominant 87.5% (n = 7). The history of chronic smoking wasfound in four patients. The main carcinogenic risk factor identified in our patients was urogenital bilharzia (6 cases / 8).The histological type found was urothelial carcinomain 12.5% (n = 1) and invasive squamous cell carcinomain 87.5% (n = 7). Transurethral resection of the tumor was performed in 62.5% (n = 5). Endoscopic biopsy was performed in 37.5% (n = 3). The tumor was classified pT2N0M0 in 50% (n = 4), pT3aN0M0 in 37.5% (n = 3) and pT3bN0M0 in 12.5% (n = 1). Neoadjuvant chemotherapy with paclitaxel - carboplatin every three weeks was administered to all patients. The results of radiochemotherapy (see Table: evolution). CONCLUSION: Concomitant radiochemotherapy is a conservative curative treatment that can be proposed as a replacement for cystectomy, for non-metastatic infiltrating tumors after the most complete endoscopic resection.

OBJECTIF: Le but de cette étude était de décrire les résultats d'une radiochimiothérapie chez les patients après résection transurétrale des tumeurs de vessie infiltrant le muscle. MATÉRIEL ET MÉTHODES: Une étude rétrospective allant de mai 2014 à mai 2016 au service de radiothérapie de l'hôpital du Mali. Ont été inclus, tous les patients présentant un cancer de vessie infiltrant le muscle. Les cancers secondaires de la vessie ainsi que les formes métastatiques ont été exclus de notre étude. La résection transurétrale de vessie a été réalisée. La chimiothérapie néoadjuvante à base de paclitaxel ­ carboplatine a été administrée toutes les trois semaines. La radiothérapie externe au photon 6MV à la dose de 66 Gy en raison de 2 Gy de 5 séances par semaine associée à la chimiothérapie concomitante à base de cisplatine (CDDP) 40mg/m2/semaine a été réalisée. RÉSULTATS: Au total huit patients ont été inclus dans notre étude. L'âge moyen de 53,75±14,84 ans. Le sexe masculin était prédominant 87.5% (n=7). L'antécédent de tabagisme chronique était retrouvé chez quatre patients. Le principal facteur de risque cancérigène identifié chez nos patients était la bilharziose urogénitale (6cas/8). Le type histologique retrouvé était le carcinome urothelial dans 12.5% (n=1) et le carcinome épidermoïde infiltrant dans 87.5% (n=7). La résection transurétrale de la tumeur a été réalisée dans 62.5% (n=5). La biopsie par voie endoscopique été réalisée dans 37.5% (n=3). La tumeur été classée pT2N0M0 dans 50% (n= 4), pT3aN0M0 dans 37.5% (n=3) et pT3bN0M0 dans 12.5% (n= 1). La chimiothérapie néoadjuvante à base de paclitaxel ­ carboplatine chaque trois semaines a été administrée chez tous les malades.Les résultats de la radiochimiothérapie (cf. Tableau: évolution). CONCLUSION: La radiochimiothérapie concomitante est un traitement curatif conservateur qui peut être proposée en remplacement à la cystectomie pour les tumeurs infiltrantes non métastatiques après une résection endoscopique la plus complète possible.

[Neoadjuvant chemotherapy in locally advanced cervical cancer in patients receiving a concomitant chemoradiotherapy in a low income country]. / Chimiotherapie neo adjudante dans les cancers localement avances du col uterin chez des patientes recevant une radiochimiotherapie concomitante dans pays aux ressources limitees.

PURPOSE: Delays to access to radiotherapy are long in our context. The purpose of this study was to analyze the effect of neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancers. PATIENTS AND METHODS: We conducted a retrospective study from April 2014 to April 2016 at the radiotherapy center of "Hopital du Mali" in Bamako, Mali. Patients were allocated according to age, histological type, tumor size and the 2002 classification of the FIGO. Experimental protocol was the administration of a neoadjuvante chemotherapy with association of Paclitaxel 175mg/m2 + Carboplatine AUC 5 every 3 weeks and radiothérapy cure with avec linac 6 MV at 70 Gy due to 5 sessions of 2 Gy per week associated with a concomitant chemotherapy with cisplatin at 40 mg/m2/week. The clinical response was assessed at the end of neoadjuvant chemotherapy and of concomitant chemoradiotherapy. RESULTS: Thirty patients were included in the study. The mean age was 53.63 ± 8.9 years. The mean size of the tumor was 5.17 cm (2 to 7 cm). According to the 2002 classification of the FIGO stages IIB were 33% (n = 10); IIIB were 57% (n = 17) and IVA were 10% (n = 3). Clinical evaluation at the end of neoadjuvant chemotherapy found: complete response 17 % (n = 5), partial response 10% (n = 3) and stable disease 73 % (n = 22). Evaluation at the end of the concomitant chemoradiotherapy had found the complete response in 90% (n = 27) and stable disease in 10% (n = 3). CONCLUSION: Neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancer allows stabilization of the tumor and improves local control. Due to long delays to access to radiotherapy treatment in our context; neoadjuvant chemotherapy is an alternative to stabilize the disease and prevent distant metastasis from locally advanced cervical cancers.

OBJECTIF: Les délais d'attente pour accéder à la radiothérapie sont longs dans note contexte. L'objet de cette étude était d'analyser le résultat de la chimiothérapie néo adjuvante à la radiothérapie dans les cancers localement avancés du col utérin. PATIENTS ET MÉTHODES: Nous avons réalisé une étude rétrospective allant d'avril 2014 à avril 2016 au centre de radiothérapie de l'hôpital du Mali. Les patients ont été regroupés selon l'âge, le type histologique, la taille de la tumeur, la classification de la FIGO 2002. Le schéma thérapeutique était une chimiothérapie néo adjuvante associant Paclitaxel 175 mg/m2 et Carboplatine AUC 5 toutes les 3 semaines suivie d'une radiothérapie avec linac 6 MV à la dose de 70 Gy en raison de 5 séances de 2 Gy par semaine faite concomitamment à une chimiothérapie avec du cisplatine à la dose de 40 mg/m2/semaine. La réponse clinique était évaluée à la fin de la chimiothérapie néoadjuvante et de la radiochimiothérapie concomitante. RÉSULTATS: Trente patientes ont été incluses dans l'étude. L'âge moyen était de 53.63 ± 8.9 ans. La taille moyenne de la tumeur était de 5,17 cm (2 à 7 cm). Selon la classification FIGO 2002, 10 (33%) étaient en stade IIB distal, 17 (57%) étaient en stade IIIB et 3 (10%) en stade IVA. L'évaluation clinique à la fin de la chimiothérapie néo adjuvante avait retrouvé 17 % de réponses complètes (n=5), 10% de réponses partielles (n=3) 73 % d'évolutions stables (n=22). L'évaluation à la fin de la radiochimiothérapie concomitante avait trouvé une réponse complète chez 27 patientes (90%) et une maladie stable chez 3 (10%). CONCLUSION: La chimiothérapie néo adjuvante à la chimioradiothérapie concomitante dans les cancers localement avancés du col utérin permet la stabilisation de la tumeur et améliore le control local. En raison des délais d'attente longs pour accéder à la radiothérapie, la chimiothérapie néo adjuvante est une alternative pour stabiliser la maladie et réduire le risque de métastases à distance des cancers du col utérin localement avancés.

Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

OBJECTIVES: To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)(5) GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. METHODS: Cross-sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. RESULTS: Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non-responders [(NANP)(5) (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46-0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48-0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50-1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32-0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38-1.05; P = 0.08). CONCLUSION: Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.

[Management of pain of acute sickle cell pain crises by health care providers in Mali]. / La gestion de la crise drépanocytaire par les agents de santi au Mali.

The most common form of sickle cell disease is characterized by frequently recurring pain crises. Success in managing these crises can be considered a measure of the quality of life in patients with sickle cell disease. There is a paucity of data on the level of care and quality of management of pain crises in sickle cell patients in Africa. The purpose of this study was to assess these two parameters in Mali. Data were collected by interview using a validated individual survey form. Analysis of data demonstrated that sickle cell crises were being managed at all levels of the health care system by practitioners with differing competency levels. Management did not follow a single algorithm. Vasodilators were the most commonly prescribed medications. Major analgesics were prescribed by fewer than 10% of the practitioners surveyed. Blood transfusion appeared to be overused. Based on these findings we conclude that strategies to improve management of sickle cell pain crises must recognize the urgent need for training health care providers to use standardized algorithms of proven efficacy.

Effectiveness, safety, and cost of partial exchange transfusions in patients with sickle-cell anemia at a sickle cell disease center in sub-Saharan Africa.

The partial exchange transfusions necessary for management of some sickle-cell complications raise the issue of effectiveness in the context of limited resources and inadequate blood safety. This study evaluated the effectiveness, safety, and cost of partial exchange transfusions in 39 patients with sickle-cell anemia in Lubumbashi, looking at the patients' age and gender and the tolerability and direct cost of the transfusions. Excel and SPSS 18 were used for data entry and analysis. Chi2 and Fisher exact tests were used for comparisons. A P-value ≤ 5% was considered statistically significant. The average age of patients was 8.6 ± 6.4 years, and the majority were girls. The most frequent indications were stroke, severe infections, severe vasooclusive crises, and acute chest syndrome. Partial exchange transfusions were effective in improving hemoglobin and hematocrit as well as the percentage of HbS. No acute accident was observed during any partial exchange transfusion; one anti-Kell alloimmunization and 2 cases of iron overload were observed. The annual cost of partial exchange transfusions per patient requiring (and able to afford) regular treatment was US $ 3,345 without iron chelation and more than US $ 5000 with chelation. Partial exchange transfusions are effective and tolerated, but financially inaccessible to the majority of our sickle cell patients. Thus, an assessment is needed of the economic burden of sickle cell complications that require partial exchange transfusions in the context of countries with limited financial resources.

[Prevalence and risk factors for sickle retinopathy in a sub-Saharan comprehensive Sickle Cell Center]. / Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d'Afrique subsaharienne.

INTRODUCTION: Retinopathy is a chronic complication with severe functional consequences in patients with sickle cell disease. Its prevalence is not well known in sub-Saharan Africa because of the absence of screening. We report here the results of a routine screening for sickle retinopathy in a Comprehensive Sickle Cell Center in Sub-Saharan Africa. METHODS: Screening of sickle retinopathy was carried out in all sickle cell patients aged 10 and over, followed between 2010 and 2012. Retinopathy was screened by dilated indirect fundoscopic examination and retinal angiography, if necessary. The gender, age and hematological parameters of patients with sickle retinopathy were compared with those of controls randomly selected from the cohort of sickle cell patients without retinopathy followed during the same period. RESULTS: The overall prevalence of sickle cell retinopathy was 8.8% (142/1604): 12.4% (91/731) in SC, 5.2% (38/734) in SS, 9.4% (5/53) in Sß°-thalassemia patients and 9.3% (8/86) in Sß+-thalassemia patients. Proliferative retinopathy was more common in SC patients (P<0.01). High levels of hemoglobin or of hematocrit were associated with retinopathy in all patients and with proliferative retinopathy in SC patients. In SS or Sß0thalassemia patients, high leukocyte count was associated with proliferative retinopathy. Low fetal hemoglobin level was associated with retinopathy in all groups. CONCLUSION: The prevalence of sickle cell retinopathy is high and negatively associated to the level of fetal hemoglobin. The efficiency of a routine screening for sickle cell retinopathy must be assessed in Africa as well as the benefit of phlebotomy and hydroxyurea therapy as a preventive treatments.

[Screening of cerebral vasculopathy in sickle cell anemia children using transcranial Doppler]. / Dépistage de la vasculopathie cérébrale drépanocytaire par doppler transcrânien au Mali.

Cerebral vasculopathy exposes patients to a high risk of stroke, a major complication of sickle cell disease (SCD) associated with a high risk of death and disability. Transcranial doppler (TCD) ultrasonography used to identify SCD patients at risk of stroke may contribute to significantly reducing morbidity and mortality in these patients by indicating appropriate treatment. From March 2008 to February 2013, we conducted systematic screening for cerebral vasculopathy using TCD in 572 SCD patients (including 375 SS, 144 SC, 26 S/ß(0), and 27 S/ß(+) thalassemia patients) aged 1-17 years in a comprehensive center for follow-up and research on sickle cell disease in Bamako, Mali. After exclusion of 30 inadequate results and one case of abnormal TCD observed in a multiple organ failure patient, we found an abnormal or conditional TCD in 18% of 541 children examined in a steady state. The highest prevalence of abnormal cases concerned homozygous SS patients (8.1%). No case of abnormal or conditional TCD was observed in children with S/ß(+) thalassemia. Hemoglobin concentrations were significantly lower in patients with conditional or abnormal TCD (P<0.01). In a subgroup of 68 patients with conditional TCD, nine (13%) converted to abnormal TCD over 1 year. In this subgroup of 68 conditional TCD patients, a decrease or increase in baseline hemoglobin concentration was predictive of conditional or abnormal TCD at the follow-up visit. Progression towards conditional TCD was observed in four patients (0.9%) who initially had normal TCD. Children with abnormal TCD had, whenever possible, a monthly exchange transfusion program. One case of transient stroke in the context of P. falciparum malaria with low hemoglobin concentration and one death were observed. These findings highlight the need for systematic TCD in sickle cell disease monitoring and implementing regular blood transfusion programs in the context of limited access to regular and secure blood transfusions.

Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa.

Eighteen patients hospitalized with intestinal parasitic infections associated with diarrhea and dehydration completed a study of nitazoxanide in the treatment of Cryptosporidium parvum and other intestinal parasitic infections. Seventeen of the 18 patients were positive for human immunodeficiency virus. Twelve patients were diagnosed with clinical Stage 4 acquired immunodeficiency syndrome (AIDS) according to the 1990 World Health Organization proposed clinical classification system and cryptosporidiosis. Nitazoxanide (500 mg tablets) were administered orally, one tablet twice a day for seven consecutive days. Cryptosporidium parvum oocysts were eradicated or reduced by more than 95% in seven of the 12 Stage 4 AIDS patients who completed the study based upon two post-treatment fecal examinations conducted on days 7 and 14 following the initiation of treatment. The elimination or reduction of C. parvum oocysts was associated with a complete resolution of diarrhea in four of the seven patients. The test drug was also effective against cases of Isospora belli, Entamoeba histolytica, Giardia lamblia, Ascaris lumbricoides, Enterobius vermicularis, Hymenolepis nana, and Dicrocoelium dentriticum. Treatment with nitazoxanide was well tolerated by the patients. There were no abnormalities in blood chemistry or hematology data that were considered to be attributable to nitazoxanide therapy. Transient episodes of vomiting were observed in four patients, all with Stage 4 AIDS and cryptosporidiosis, which resolved spontaneously without discontinuation of treatment and were not considered to be related to administration of nitazoxanide.

PIP: The effectiveness of nitazoxanide in the treatment of Cryptosporidium parvum and other intestinal parasitic diseases was assessed in 18 patients hospitalized at Point G. National Hospital in Bamako, Mali, with parasite-related diarrhea, dehydration, and weight loss. 17 of the 18 patients were infected with HIV, and 12 of these had progressed to clinical stage 4 AIDS. 500 mg tablets of nitazoxanide were administered twice a day for 7 days. After completion of treatment, Cryptosporidium parvum oocysts were eradicated or reduced by more than 95% in 7 of the stage 4 AIDS patients; diarrhea was completely resolved in 4 of these patients. Nitazoxanide was also effective against other parasites common in AIDS patients, including Entamoeba histolytica, Giardia lamblia, and Isospora belli. The test drug was well tolerated by all recipients, with no blood chemistry abnormalities.

Chloroquine treatment of uncomplicated Plasmodium falciparum malaria in Mali: parasitologic resistance versus therapeutic efficacy.

Whether and when to replace chloroquine with other antimalarial drugs is an urgent public health question in much of Africa, where Plasmodium falciparum, which is increasingly resistant to chloroquine, continues to kill millions each year. Antimalarial drug efficacy has traditionally been measured as parasitologic resistance, but recent guidelines use both clinical and parasitologic criteria to monitor therapeutic efficacy. To assess the new efficacy protocol, we measured parasitologic and therapeutic outcomes in 514 patients treated with chloroquine for uncomplicated P. falciparum malaria in Mali. There was a general agreement between parasitologic and therapeutic outcomes at two sites, with 13-17% parasitologic resistance rates and 10-15% treatment failure rates. However, the new protocol overestimated early treatment failure rates (21-71% of cases classified as early treatment failure had sensitive or RI parasitologic responses), particularly where resistance was rare, and missed low-level parasitologic resistance. Modifications of the protocol for monitoring antimalarial therapeutic efficacy are recommended.

Comparison of two methods for assessing child mortality in areas without comprehensive registration systems.

We compared the effectiveness of 2 approaches to assessing child deaths in a rural area of Burkina Faso, West Africa. Censuses, repeated yearly, identified 410 child deaths in the age range 6-59 months. Surveillance using community informants identified only 319 deaths. The estimated sensitivities of the 2 systems were 97% and 76%, respectively. Both systems appeared less effective at detecting child deaths before 6 months of age (sensitivities 74% and 57%). Most of the deaths missed by the census were of children born since the previous census. The cost of one year's surveillance was twice that of a single census. The marginal cost of the surveillance system per additional child death identified between 6 and 59 months was about US$ 1500. Thorough annual censuses may be sufficient to ascertain almost all child deaths over 6 months of age. In studies wishing to identify child deaths before 6 months of age, such an approach is unlikely to be adequate. In such situations, our data indicated that the use of unpaid community informants can improve assessment of deaths. Where accurate assessment of early infant death rate is required, regular visits to each household by members of the study team are likely to be the only reliable approach.

Case report: life-threatening hypoglycaemia associated with sulfadoxine-pyrimethamine, a commonly used antimalarial drug.

Due to chloroquine resistance, several African countries have changed their first-line malaria treatment to sulfadoxine-pyrimethamine (SP). In this report, we present a case of hypoglycaemic coma associated with SP, an adverse reaction that is likely to be underreported and expected to occur with greater frequency as the use of SP increases.

Insecticide-treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso.

Insecticide-treated bednets and curtains have been shown to be successful in reducing malaria transmission and child mortality in Africa over periods of up to 2 years. A major concern relating to this approach is that, in time, it will be compromised by the selection of mosquito genotypes that are resistant at the biochemical or behavioural level. We report entomological data from a large area in Burkina Faso where insecticide-treated curtains have been in use for up to 5 years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4 sentinel villages. In addition cross-sectional surveys using indoor spray catches and outdoor CDC light-trap catches were performed each September in a larger number of villages, including 8 located outside the intervention area. We found no evidence of the selection of mosquito phenotypes that might compromise the intervention. Indoor and outdoor vector densities remained very low after 5 years of intervention, both compared with pre-intervention levels and with concurrent levels outside the intervention area. We found no evidence of a switch to outdoor rather than indoor biting. The proportion of blood meals taken on humans may have decreased but our data are inconclusive on this point. We observed higher vector densities and sporozoite rates at the periphery of the intervention zone than at the centre, which may reflect re-invasion of peripheral villages by mosquitoes from outside the intervention area. In 'real life' programmes, with perhaps patchy, less than optimal coverage, the protection against malaria transmission provided to individuals using insecticide-treated materials may be less than that achieved in the randomized controlled trials which demonstrated an impact of insecticide-treated materials on child mortality.

Wide-scale installation of insecticide-treated curtains confers high levels of protection against malaria transmission in a hyperendemic area of Burkina Faso.

In a region of Sudanese savannah in Burkina Faso, insecticide-treated curtains were installed in 8 out of 16 zones, each covering an area of about 50 km2. Longitudinal entomological monitoring using CDC light traps was performed in 4 villages (2 intervention, 2 control) over a period of 3 years (including 1 year prior to intervention). In the 3rd year a cross-sectional entomological survey using spray catches was performed in 84 villages (40 intervention). Indoor vector densities in protected houses showed large reductions (P = 0.01). The available data were also consistent with an impact on outdoor and unprotected indoor densities. The proportion of mosquitoes carrying sporozoites was 4.1% in protected villages compared with 11.5% in unprotected villages (P = 0.07). Entomological inoculation rates fell substantially (P = 0.01), reflecting these reductions. The impact of this intervention on mosquito survival appears to have been greater than those in similar trials conducted in the Gambia, Ghana and Kenya in which the intervention was applied over smaller areas.

A comparison of the incidence of severe malaria in Malian children with normal and C-trait hemoglobin profiles.

Although a protective effect against malaria has been demonstrated for several hemoglobin variants, no selective factor is established for the high incidence of HbC in regions of West Africa. Here we report a survey of hemoglobin profiles among children admitted with symptomatic and severe malaria to the Gabriel Touré Hospital in Bamako, Mali, where the frequency of the HbC gene is 8-10%. Children with AC and AA profiles presented with severe malaria at comparable rates, indicating lack of protection by the heterozygous state. Two admitted children, one of whom presented with cerebral malaria, were found to have SC profiles. No CC homozygotes were detected in the study cohort.

Humoral responses to defined malaria antigens in children living since birth under insecticide treated curtains in Burkina Faso.

Insecticide treated materials (ITM) are considered a useful malaria control measure for endemic countries, but whether they also delay the acquisition of immunity to malaria remains unclear. This study investigates plasma antibody levels in 160 children aged 3-6 years from five villages protected by insecticide treated curtains (ITC) over 6 years and in 184 children of the same age group from five villages in the same area never covered by ITC. The antigens to which antibodies were investigated were: the Plasmodium falciparum circumsporozoite protein (CSP) repetitive sequence (NANP)5; the C-terminal domain of the P. falciparum exported protein 1 (Cter-PfExp1); three fragments of the glutamate rich protein (GLURP), referred to as R0, R1 and R2; the merozoite surface protein 3 (MSP3). The level of antibodies was lower in children from the ITC area than in children from the non-ITC area for (NANP)5, R0, R2 and MSP3. Prevalence and intensity of P. falciparum infection were similar in the two groups of children. These findings suggest that reducing the level of malaria transmission over a long period may affect the level of antibodies in children to both sporozoite and blood stage malaria antigens.

Different response to Plasmodium falciparum in west African sympatric ethnic groups: possible implications for malaria control strategies.

The comparison of malaria indicators among populations with different genetic backgrounds and uniformly exposed to the same parasite strains, is one of the approaches to the study of human heterogeneities in the response to the infection. The results of our comparative studies conducted in Burkina Faso, West Africa, showed consistent interethnic differences in Plasmodium falciparum infection rates, malaria morbidity, prevalence and levels of antibodies to various P. falciparum antigens, and genetic background. The differences in the immune response were not explained by the entomological observations which indicated substantially uniform exposure to infective bites. The presence in the same epidemiological context of individuals characterized by different immune reactivity to malaria represents an ideal opportunity to study the possible relationships between the baseline level of anti-malaria immunity of a population and the protective efficacy of control measures based on the reduction of transmission. In spite of similar reduction of entomological inoculation rates obtained by permethrin-impregnated curtains, ethnic- and age-dependent efficacy was observed. These studies demonstrate the existence of marked interethnic differences in the susceptibility to P. falciparum malaria, probably involving the genetic regulation of humoral immune responses. These differences should be considered in the development of anti-malaria vaccines and in the evaluation and application of malaria control strategies.

Widespread distribution of insecticide-impregnated curtains reduces child mortality, prevalence and intensity of malaria infection, and malaria transmission in rural Burkina Faso.

The results of the first two years of implementation of a large scale trial of insecticide-treated curtains in Burkina Faso are summarised in this presentation. The trial was conducted in a highly malarious area and involved a population of slightly less than 100,000, distributed in 158 villages over an area of almost 1000 km2. A remarkable impact on entomological parameters (Anopheles density, sporozoite rate, entomological inoculation rate) was accompanied by a relatively modest reduction of parasitological indices (prevalence and density of Plasmodium falciparum). All-cause mortality in children 0.5 to 5 year old showed over two years a 15% decline. The authors believe that the wide surface of the protected zone and the almost total coverage achieved in the intervention villages were the major determinants of the observed reduction of transmission. A conclusive interpretation of the mortality results requires a further follow-up of the study population.

Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial.

OBJECTIVE: To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa. DESIGN: Randomised, double blind, placebo controlled efficacy trial. SETTING: 18 villages in rural northwestern Burkina Faso. PARTICIPANTS: 709 children were enrolled; 685 completed the trial. INTERVENTION: Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for six days a week for six months. MAIN OUTCOME MEASURES: The primary outcome was the incidence of symptomatic falciparum malaria. Secondary outcomes were the severity of malaria episodes, prevalence of malaria parasite, mean parasite densities, mean packed cell volume, prevalence of other morbidity, and all cause mortality. RESULTS: The mean number of malaria episodes per child (defined as a temperature >/=37.5 degrees C with >/=5000 parasites/microliter) was 1.7, 99.7% due to infection with Plasmodium falciparum. No difference was found between the zinc and placebo groups in the incidence of falciparum malaria (relative risk 0.98, 95% confidence interval 0.86 to 1.11), mean temperature, and mean parasite densities during malaria episodes, nor in malaria parasite rates, mean parasite densities, and mean packed cell volume during cross sectional surveys. Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause mortality was non-significantly lower in children given zinc compared with those given placebo (5 v 12, P=0.1). CONCLUSIONS: Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa, but it does reduce morbidity associated with diarrhoea.