Effectiveness of seasonal malaria chemoprevention (SMC) treatments when SMC is implemented at scale: Case-control studies in 5 countries.

BACKGROUND: Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. METHODS AND FINDINGS: Case-control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3-59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%-50.9% and 38.9%-46.9% of controls and cases, respectively, were male. In all 7 individual case-control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29-42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: Protective effectiveness 90% (95% CI: 79%, 96%; P<0.001), and 59% (95% CI: 34%, 74%; P<0.001) for SMC 0-28 days and 29-42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources. CONCLUSIONS: SMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case-control design used in this study can be used at intervals to ensure SMC treatments remain effective.

Impact of repeated NeemAzal-treated blood meals on the fitness of Anopheles stephensi mosquitoes.

BACKGROUND: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. METHODS: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. RESULTS: A dose and frequency dependent impact of NeemAzal treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 - 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group respectively. CONCLUSIONS: The findings of this study, taken together with the accumulated knowledge on neem open the challenging prospects of designing neem-based formulations as multi-target phytomedicines exhibiting preventive, parasite transmission-blocking as well as anti-vectorial properties.

A user friendly method to assess Anopheles stephensi (Diptera: Culicidae) vector fitness: fecundity.

Fecundity, bloodmeal size, and survival are among the most important parameters in the overall fitness of mosquitoes. Impact of an intervention that affects fecundity can be assessed by directly counting the eggs laid by exposed mosquitoes, which is usually done manually. We have developed a macroinstruction, which can be used to count thousands of Anopheles stephensi Liston eggs in a few minutes, to provide an alternative and adaptable method to egg counting as a measure of fecundity. The macro was developed using a scanner and a computer running AxioVision Rel. 4.8 software, a freely accessible software compatible with Windows XP/7/Vista. Using this semiautomated method, it is possible to reduce time, avoid human error and bias, and obtain improved consistency in studies measuring mosquito fecundity.

Misdiagnosis of malaria using wrong buffer substitutes for rapid diagnostic tests in poor resource setting in Enugu, southeast Nigeria.

Background: A key to the effective management of malaria is prompt and accurate diagnosis, and the use of malaria rapid diagnostic tests (mRDTs) is becoming relevant in the absence of reliable microscopy. This study explored the phenomenon of using the wrong buffer vial (often a kit from another brand or buffer from HIV rapid test kits), dextrose, saline or distilled water among health care providers who used RDTs for malaria diagnosis in resource poor settings in Enugu South East, Nigeria. Materials and Methods: Laboratory personnel (medical laboratory scientists, technicians, assistants, nurses, community health extension workers (CHEW), community health officers (CHO) and doctors) were interviewed using structured questionnaires and results were checked using the SOP checklist. The selection criterion was a prior experience with using RDTs, and any facility that did not use RDTs was excluded. Results: Of the 80 study participants that completed their questionnaires, 56.3% reported that malaria diagnosis was positive using non-buffer RDTs detection while others reported negative results. Among the various professionals who used RDTs, 76.2% reported to have run out of RDT buffer stock at least once. Of the study participants that ran out of RDT buffer solution, 73% declared to have used non-RDT alternatives (physiological saline, 0.9% NaCl), distilled water, HIV buffer or ordinary water). Only 30% had received formal training on the proper usage and application of RDTs while 70% had never received any formal training on RDTs but learnt the technique of using RDT on the job. Conclusions: This study demonstrated that at least three quarters of health care workers in a resource poor setting had run out of buffer when using malaria RDTs and that the majority of them had used buffer substitutes, which are known to generate inaccurate tests results. This has the consequence of misdiagnosis, thus potentially damaging the credibility of malaria control.

Impact of Plasmodium falciparum and hookworm infections on the frequency of anaemia in pregnant women of rural communities in Enugu, South East Nigeria.

INTRODUCTION: Malaria and hookworm infections are common in sub-Saharan Africa and they increase the prevalence of anaemia in pregnancy with resultant poor pregnancy outcomes. This study was carried out to assess the impact of Plasmodium falciparum and hookworm infections on the frequency of anaemia among pregnant women in two rural communities in Enugu, South East Nigeria. METHODS: A cross sectional descriptive study was carried out in a total of 226 women attending antenatal clinics at two rural Primary Health Centres (PHC) from April 2011 to July 2011(each PHC with 113 subjects). Socio-demographic data were collected through a structured questionnaire. Blood and stool samples were evaluated for haemoglobin estimation and malaria parasites, and stool samples examined for parasitic infection in all the women. Data was analyzed using STATA 10 software statistical analysis package. Student t-test was used for comparing mean values and chi square test for comparing categorical variables and level of significance set at p<0.05 and logistic regression was used to identify the risk factors associated with malaria in pregnancy. RESULTS: The mean age of the women was 27 years with range 18-38 years and SD of 5 years. Most of the women were housewives and over 50% in their second trimester. 53% of them had malaria parasites while 27% had hookworm infection. About 40% of the women were anaemic (haemoglobin<0.001). Similar association was found between hookworm infection and anaemia (p<0.001). Though both malaria and hookworm infections greatly increase the odds for anaemia (AOR 18.06, CI 18.15 -39.99, P<0.001) and (AOR 5.28, CI 2.26-12.38, P<0.001) respectively, the odds for having anaemia in pregnancy was higher for malaria than hookworm infections. CONCLUSION: Plasmodium falciparum and hookworm infections have significant impact on the high frequency of anaemia in pregnancy in our rural communities. There is need to strengthen the control program that has been in place with an integrated intervention to combat these parasitic infections in our rural communities, with mass distribution of antihelminthics as one of the included relevant methods, among others.

Does Pre-Survey Training Impact Knowledge of Survey Administrators and Survey Outcomes in Developing Countries? Evaluation Findings of a Training of Trainers Workshop for National AIDS and Reproductive Health Survey-Plus in Nigeria.

BACKGROUND: Although, Nigeria had conducted various national surveys followed by central and state level trainings for survey administrators, prior pre-survey trainings have not been systematically evaluated to assess their impact on knowledge gain and final outcome of the survey. A central training of trainers' session was organized for master trainers on the conduct of the 2012 National AIDS and Reproductive Health Survey. OBJECTIVES: To evaluate the impact of training on the quality of conduct of a national research survey in the 36 states and the Federal Capital Territory in Nigeria. METHOD: A total of 185 participants consisting of State AIDS Program Coordinators, Reproductive Health Coordinators, State Laboratory Scientists, Lead Supervisors and Counselor Testers were invited from the 36 states in Nigeria and the FCT for the central training of trainers in Abuja. The training lasted 5 days and the trainees were grouped into two on the basis of behavioral epidemiology and laboratory components. Training tools such as the developed protocol, training power point slides, practical sessions such as role plays, and usage of HIV rapid test kits were utilized during the training. The facilitators were drawn from Federal Ministry of Health (FMoH), universities and research Institutions as well as Non-Governmental Organizations (NGOs). The facilitators prepared and administered 25 structured questions for the behavioral group and 28 questions for the laboratory group at the beginning of the training to assess the participants' knowledge of HIV and the survey. The same questions answered by Trainees responded to the same questions prior to the commencement and at the end of the trainings. Scores were aggregated to 100 for each test. We conducted paired t-test to determine statistically significant differences between pre-test and post-test results at 0.05 significance level and ANOVA to determine if there were differences in knowledge level among different groups. RESULT: The overall mean pre-test and post-test scores were 64.0% and 77.4% respectively indicating a 13.4% knowledge gain above what it was at the beginning of the training. The mean pre-test score and post-test score for the Southern states (SN) were 64.7% and 80.3% while that of the Northern states (NN) were 63.5% and 75.3% representing a knowledge gain of 15.6% and 11.8% respectively. There was statistical significant difference in the post-test scores between the two regions (p=0.001) and in knowledge gained after the training (p=0.017). CONCLUSIONS AND PUBLIC HEALTH IMPLICATIONS: Comparison between the pre test and post test scores at the 5-day training showed a significant gain in knowledge of participants. The survey training contributed positively to the preparation and building of knowledge needed for the conduct of 2012 NARHS-plus.