Study design
A community–based, unmatched case–control study was conducted in the Baish governorate in Jazan region of Saudi Arabia. Data were collected from case investigations/reactive case detection (RCD) carried out by malaria and vector control program in Baish Malaria Centers in Jazan Provinces, Saudi Arabia. The study utilized the existing resources of the program and recruited trained staff from the malaria elimination program.
Cases were defined as subjects who reported to the malaria center in Baish with a confirmed positive thick and/or thin blood smear or rapid diagnostic test high risk (RDT[1]) from the local hospital, primary health center, or malaria center. All case investigations/reactive case detection (RCD) carried out by the study-trained staff in Baish malaria elimination center during the study period were included. Controls were randomly selected from the community members living near clinical cases (index cases) within a radius of 500 m village. However, they did not live in the same household, and a random selection will take place; every third person who will be screened for malaria during the RCD who test malaria negative will be eligible to join the study and asked to join the study.
Controls are defined as subjects screened during the case investigation whose RDTs were negative for Plasmodium infection (additionally, thin blood smear were reviewed later for confirmation) and lived in the same village but do not live in the same household or work on the same farm. The selected eligible candidates were consented to join the study and asked to answer the questionnaire.
Study site
Baish malaria control center is one of the nine malaria control centers in Jazan region(5). It serves as a head office for two governorates Baish and Al–Rayth. It oversees five peripheral malaria and vector control facilities that all together deliver malaria control activities in one of the region’s most significant agricultural areas, occupying 23% of Jazan total area (an area of approximately 7,500 hectares (ha) of agriculture area) (Figure 1)(38). Baish is in the valley of Baish in Tihamah lowland plain at 400–600 m elevation above sea level near the Red Sea coast (38). The valley contains more than 90 water streams, where more than 455 villages are scattered, prone to flooding during the rainy season(14). It is also where the tallest dam in Saudi Arabia was constructed at 106 m (348 ft.) in height. It is used for irrigation and groundwater recharge to supply the surrounding agriculture(14). The current population is 77,442 people(39). Residents are mainly engaged in agricultural activities such as growing coffee, millet, corn, maize, mangoes, bananas, fruits, and vegetables; raising domestic livestock (sheep, goats, camels, cows, and poultry); and handicraft work such as ceramics, pottery, and leather goods (40). Malaria and vector control center is in Alhaqo area, the famous historic land route that connects Yemen–Jazan–Jeddah. Travel to Jazan city is possible through well-paved road. However, the network between areas and surrounding villages is a mix of paved and unpaved roads(41).
Malaria transmission is seasonal during the rainy season (October–April). Malaria transmission peaked in January (42), mainly during the winter. Plasmodium falciparum (P. falciparum) predominates malaria transmission (5). The primary malaria vector is An. arabiensis, the only positive vector for malaria in southern Saudi Arabia (3, 43) with a sporozoite rate (0–0.7%) (5). Population vector presents in low density during autumn through spring and peaks during winter following the rainy season(5). The natural habitat for An. arabiensis are valleys and rain pools, but it also can be found in domestic water containers and rock pools (shallow water with pH7–9)(44). Adult mosquitoes exhibit both endophagic and exophagic biting behavior (45). Interestingly in a study by Al–sheikh et al., only 40% of bloodmeals were of human origin (44, 46, 47). An. arabiensis feeds and rests both indoors and outdoors. For this reason, current vector control methods targeting households, such as indoor residual spraying and insecticide-treated nets, or long-lasting insecticidal nets, may not sufficiently mitigate transmission events that occur in outdoor settings (48-51).
Inclusion and exclusion criteria
Inclusion criteria for the study were individuals who are reported to Baish malaria centers in Jazan Provinces during two rainy seasons from (Aug 2017–Jan 2018) – (Aug 2018–Jan 2019) dates RDT-confirmed malaria cases were successfully traced to their households and enrolled in the study. Saudi Arabia and are part of case investigations/reactive case detection (RCD), age ten years and older[2], both male and female with history of confirmed malaria infection, and received a Giemsa stained thick and thin blood smear or RDT for malaria diagnosis.
Exclusion criteria for the study were: individuals under 10 years old, have history of malaria in the last 30 days (excluding the current episode), used malaria chemoprophylaxis or treatment in the last 30 days, or were residents of Jazan for less than two weeks (52).
Sample size determination and recruitment
Sample size calculations were conducted in Open Epi, Version 3[3]. The study was powered to detect an odds ratio of 2.0 with two–sided confidence level 95% and 80% power (chance of detection) on the measure of a night spent away from the home town in the last month, assuming that 20% of those who were not infected with any parasite species had travelled overnight in the past month, and a ratio of control to case 1:4. In total, a sample size of 484 individuals was needed; these consisted of 97 cases (positive persons for malaria infection) and 387 controls (negative persons for malaria infection).
Data collection
Participants were recruited over a 20–week period during case investigations/reactive case detection (RCD) that was carried out by Baish malaria center by personnel fluent in the Arabic and English language. After obtaining informed consent, participants were interviewed using an Android tablet to fill a pre–tested questionnaire using Open Data Kit (ODK)[4].
ODK an extensible, open-source suite of tools designed to build information services. ODK currently provides four tools to this end: Collect, Aggregate, Voice, and Build. Collect is a mobile platform that renders application logic and supports the manipulation of data. Aggregate provides a "click-to-deploy" server that supports data storage and transfer in the "cloud" or on local servers. Designed to be used together or independently, ODK core tools build on existing open standards and are supported by an open-source community that has contributed additional tools.
Data were gathered on socio–demographics and household risk factors including travel history (where did they travel international or domestic, length of the travel, reason for travel, known malaria active transmission foci’s), bed net use, agricultural activities, and spiritual gathering (see full questionnaire in appendix C). All confirmed malaria cases were used as a case. Controls were confirmed case contacts who screened for malaria infection using RDTs and tested negative for malaria infection. Completed forms were uploaded to ODK aggregate database when internet was available. Data were converted to STATA 16.0 (Stata Corporation, Collage Station, TX, USA) format for analysis.
Data analysis
Data analysis was done using STATA version 16 (Stata Corporation, College Station, TX, USA). Descriptive statistics was used to summarize independent variables and demographics. Bivariate analysis was conducted to assess the relationship between individual characteristics and the outcome of malaria infection. Chi‐square (χ2), and Fisher’s test was used (for small–sized samples) to assess the differences in bivariate outcome. A simple wealth index was created using binary variables for durable asset possession using principal component Analysis (PCA) (53, 54). The study population was then categorized into wealth quartiles (55). Ordinal logistic regression was used to identify factors associated with the malaria infection. Factors tested include travel outside hometown in the last 30 days, currently working on animal husbandry, currently working on farming, regular attendance of spiritual gathering, and attendance of Ramadan spiritual gathering. The model also controlled for the following socio–demographic variables: age of the respondent, gender, wealth and use of ben net.
Ethical approval
Institutional Review Board (IRB) approval was obtained from Tulane University in New Orleans, Louisiana, USA and the IRB of Training and Scholarship Administration (TSA) in the Ministry of Health Jazan, Saudi Arabia.
[1] The following RDTs used in this study was RDT (InTec PRODUCTS.INC. ®, ONE STEP MALARIA (p.f/p.v) Tri–Line TEST, Xiamen, China), and/or (Bio–Rad®, OptiMAL–IT, Buckingham ,UK) confirming Plasmodium infection.