Transmission Dynamics of Residual and Re-emerging Malaria in the Amazon: Defining a Roadmap to Malaria Elimination

A population baseline longitudinal study in a major residual malaria hotspot in Brazil to: 1. identify risk factors for residual malaria infection and disease at individual and household level, 2. identify and quantify population changes in P. vivax and P. falciparum to detect reintroductions and to estimate parasite population complexity at baseline and after interventions and 3. describe changing dynamics of malaria incidence and parasitemia prevalence over time, and to assess potential effects of combinations of interventions on malaria control and elimination using mathematical models.

The study will be developed in Mâncio Lima, a residual malaria hotspot in northwestern Brazil. The population of study is approximately 2,000 subjects aged 3 months and up, who correspond to all the residents of 20% of the households of the urban area of Mâncio Lima.

Will be made Active (ACD) and Passive Case Detection (PCD) every 6 months, over 5 years. (symptom based surveying; microscopy-based diagnosis).

Each visit will include interview, physical examination and collection of 100 μL of blood (finger prick) to malaria diagnosis by smear, RDT and qPCR. If the subject will be positive by smear or RDT (rapid diagnostic test for malaria), despite of presence of symptoms, ≥ 20 mL of venous blood will be draw of them to immunology and parasite genetics study and the immediate treatment per MOH(Ministry of Health) guidelines will be performed.

Subjects with smear or RDT negative, will be followed for symptoms over the next 6 months. If it is subsequently found to be smear/RDT-positive by PCD, the treatment will be performed.

Clinical and epidemiological characteristics of malaria, genetic characteristics of the population of Plasmodium and changing dynamics of malaria transmission will be analyzed.

Cross-sectional surveys will be carried out in order to identify risk factors for residual malaria infection and disease at both the individual and household level, to supply parasite samples for detailed population-level molecular analyses and to supply epidemiological data for parameterization of new mathematical models of malaria transmission.

SPECIFIC AIMS:

* Aim 1: Longitudinally determine malaria dynamics in a major residual malaria hotspot in Brazil.
* Aim 2: Identify and quantify population changes in P. vivax and P. falciparum to detect reintroductions, and to estimate parasite population complexity at baseline and potentially after interventions.
* Aim 3: Develop and apply mathematical models to describe changing dynamics of malaria incidence and parasitemia prevalence over time, and to assess potential effects of combinations of interventions on malaria control and elimination.

  * The study will be developed in the urban area of Mâncio Lima, northwestern of Brazil.

A census performed by our field team between Nov 2015 and Apr 2016 identified \~ 10,000 inhabitants in the urban area of Mâncio Lima. At the site preparation phase, a random sample of 20% of the households enumerated during our census will be visited by our field teams and all dwellers aged 3 months or up (or their parents/guardians) will be invited to participate in the cohort study.

We expect to enroll \~ 2,000 subjects who will participate in 10 cross-sectional surveys (every six months) over five years (total of 20,000 observations), and contribute 120,000 person-months of follow-up. Because of the open-cohort design of this study, subjects who are lost for follow-up are replaced with newcomers, without affecting significantly the number of person-months of follow-up.

At each visit, the subjects will be interviewed and 100ul of blood will be collected to Active (ACD) and Passive Case Detection (PCD) (symptom based surveying; microscopy-based diagnosis). Each visit will include an interview, physical examination and collection of 100 μL of blood (finger prick) to malaria diagnosis by smear, RDT and qPCR.

When the subjects are positive by smear or RDT (rapid diagnostic test for malaria), despite of presence of symptoms, ≥ 20 mL of venous blood will be draw of them to immunology and parasite genetics study and the immediate treatment per Ministry of Health of Brazil guidelines will be performed.

Eligibility Criteria:
INCLUSION CRITERIA:

* Any subject aged 3 or more months old living in the study sites and providing written informed consent, or with parental written informed consent and assent when age-appropriate;
* Plans to remain in the study site for the next five years.

Adults and children will both contribute to the data and study goals. Adults and children will both contribute to the data and study goals. Children less than three months of age will be excluded from the study because the heel or finger prick procedures to draw blood may be perceived by the parents as inappropriate for this age group. Children aged three months or more are eligible as long as they are members of the randomly chosen households and their parents/guardians provide informed consent. Inclusion of children is essential for the study goals, since different age groups may differ in acquired immunity and therefore in the risk of having symptoms when carrying malaria parasites

EXCLUSION CRITERIA:

* any chronic or acute condition that, in the opinion of the field clinician or nurse, may affect the results of the study or the ability of providing informed consent.
* Less then 3 months old
* Do not have permanent residence in the study area