Abdisalan M Noor; Maoulid B Mohamed; Cleopatra K Mugyenyi; Mouna A Osman; Hawa H Guessod; Caroline W Kabaria; Ifrah A Ahmed; Mary Nyonda; Jackie Cook; Christopher J Drakeley; Margaret J Mackinnon; Robert W Snow

“ There have been limited opportunities for countries to assess their technical and operational strengths and weaknesses for elimination unless undertaken as part of very detailed reviews of large amounts of empirical data as implemented recently in Zanzibar, United Republic of Tanzania [ [9] .
National Malaria Indicator Surveys (MIS) have been established largely to provide milestone measurements for reaching endemic control ambitions in high to moderate transmission countries, with parasite prevalence as the main transmission indicator. ”

“ The multivariate regression model showed only age of individual and wealth of household were significantly associated with the combined P. falciparum infection and sero-prevalence (Table 3) . An increase in age group was associated with about 30% increase in P. falciparum exposure and/or infection prevalence (OR = 1.3; 95% CI = 1.2 - 1.6; p < 0.001) (Table 3) . An increase in the household wealth quintile was associated with a 20% decrease in likelihood of an individual being positive for P. falciparum antibodies or infections (OR = 0.8; 95% CI = 0.7 - 0.9; p < 0.001) (Table 3) . ”

“ Although there was a generally limited clustering of antibody/infection prevalence in Djibouti, there are 4 regions (Tadjourah, Dikhil, Obock and Ali Sabieh) which contribute to the majority of cases. However a migration from blanket coverage to targeted intervention is predicated on a robust and timely surveillance system transitioning from routine clinical treatment with incomplete monthly and quarterly reporting to a model based on daily or weekly aggressive, infectious disease surveillance supported by public awareness campaigns and universal parasitological testing. ”

“ The financial cost associated with the materials required to collect dry blood spots for serology and subsequent analysis were relatively small. The additional survey time as a result of collecting the samples on the filter papers appeared minimal. However, it was not possible to conduct a full cost-effectiveness analysis of this adaptation of a standard MIS as this was beyond the scope of this study. The biggest challenge, perhaps, is less to do with actual cost of including a serological component in standard MIS but the expertise required to implement ELISA to investigate exposure. ”

“ In Africa, some countries in the North have achieved malaria elimination in the last 30 years (Libya in 1973, Tunisia in 1979, and Morocco in 2010) and the majority of the region is largely regarded as malaria free despite a few disputed residual foci in Algeria and Egypt. ”

“ Malaria surveillance also needs to become an up-regulated disease reporting system with the ability to detect, intervene and eliminate residual foci of malaria infections as and when they emerge. The round 9 proposal includes 0.48 million USD to strengthen surveillance but deciding on how best to develop and implement malaria surveillance systems for elimination has a much weaker evidence-based platform than ITN delivery [ [3] . ”

“ This and the proposed future studies will substantially improve our understanding of malaria transmission in Djibouti, but without a carefully defined plan, staff or funding elimination of malaria in Djibouti remains only a biological possibility. The threshold of parasite prevalence seen as the benchmark for deciding whether to move on to malaria elimination or sustain low endemic control is seen as 1% parasite prevalence [3] , [11] . But to detect this level of prevalence requires large and expensive survey samples. ”

“ Use of mobile phone data to track population movements internally and externally [ [60] ; screening arriving passengers for malaria at the border entry points and recording of their detailed travel history; and redesigning household survey sampling and questionnaires to capture detailed travel histories of individuals tested for malaria infections are possible approaches to assessing the impact of human population movement on malaria in Djibouti. ”

“ The threshold for serological markers remains unclear although the absence of exposure among children under the age five years would be a good indicator that a country is approaching pre-elimination [ [3] . An alternative equivalent index is case incidence of 1 per 1000 persons at risk [ [3] , [28] . To reliably estimate this index, there is need for accurate passive and active case detection data over several years [ [11] . ”

“ The estimated required sample was 4,000 households in 160 clusters representing an estimated 24,000 individuals. The sampling indicator used to power the survey was the proportion of children under the age of five years sleeping under ITN based on the expected change from the Multiple Indicator Cluster Survey findings in 2006 [24] , predicted household size and age composition, between cluster design-effect of 1.5, 10% non-participation rate and a precision in the estimate of +/- 8.5% derived from a balance between optimized precision and costs [ [25] . ”

“ The population is spatially over-dispersed with 60% of the entire country residing in Djibouti Ville and its suburbs. Five secondary urban settlements exist outside the main city at Arta, Obock, Tadjourah, Ali Sabieh and Dikhil (Figure 1) and are inhabited by 10% of the population; the remaining 30% of the population live in villages or nomadic pastoralists scattered across 90% of the country's semi-arid, volcanic land surface in the hinterland. ”

“ We have not established P. vivax prevalence during the national survey and due to funding constraints we were not able to undertake large-scale PCR-based investigations of vivax and other rare species on the filter paper samples. ”

“ Age specific sero-prevalence plot of P. falciparum antibodies using maximum-likelihood fits from reversible catalytic equilibrium model [37] . The vertical axis shows the proportion of sero-positive individuals in each age group, the horizontal axis shows the midpoint age. Red triangles represent observed prevalence and blue fitted line is predicted age prevalence curve. ”

“ A population probability sample was used to estimate a sample of households and clusters for each of the six administrative regions reflecting the differences in urban and rural settlement within each region. ”

“ RWS is supported by the Wellcome Trust as Principal Research Fellow (#079080) . CJD acknowledges the support of the Wellcome Trust (#078925) which also supports JC. The authors are grateful to the support and diligence of the 32 field staff notably the supervisors Abdallah Mohamed, Abdillahi Ayeh, Mohamed Abakari, Abdoulkader Garad, Mohamed Moussa, Idriss Farah and Mahad Ibrahim and to Viola Kirui and Deepa Pindolia for help with data cleaning, preparation and map production. We thank Dr Tharcisse Barihuta for his advice and facilitation of the survey. ”

“ This household sub-sample was also interviewed about travel histories in the last six months, duration and destination and the presence of fever in the last 14 days and on the day of survey.
Laboratory methods Serological measures
Serologic markers can be particularly useful in areas of low endemicity, where it may be easier to detect relatively long-lasting antibody responses than a low prevalence of malaria infections in the human population or infected mosquitoes [28] - [29] . ”

“ Technical assistance was provided by the World Health Organization's Eastern Mediterranean Regional Office of (WHO-EMRO) and the Wellcome Trust, UK. We also wish to acknowledge Bart Faber and Ed Remarque of the Biomedical Primate Research Centre, Rijswijk, The Netherlands, for providing the antigen used in this study. AMN is supported by the Wellcome Trust as a Research Training Fellow (#081829) . ”

“ Morvan, D & Rodhain, F (1978) , The question of endemic malaria in Republic of Djibouti, vol. 38, pp. 299–304 CarteronBMorvanDRodhainF 1 2 [http://www.icafrica.org/fileadmin/documents/Transport_Meeting/S4-Djibouti-Ethiopia_Railway-Final-EN.pdf Financing Transport for Growth in Africa - A Brief Memorandum of the Ethiopia-Djibouti Railway] , ↑ The Ethiopia national malaria Indicator Survey 2007, 2008 ↑ Nyarango, P ”