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WHO Goodwill Ambassador's Newsletter For The Elimination Of Leprosy

REPORT: Case-finding in Brazil

Results from targeted leprosy surveillance in the Amazon region indicate the task at hand.

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Drs. Salgado, Barreto and Spencer.

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Pará State (highlighted) has some of Brazil’s highest annual new case detection rates.

Despite worldwide treatment efforts led by the WHO, the rates of transmission of leprosy in Brazil remain largely unaffected. This is evidenced by the relatively stable incidence of the disease over the last decade, with 33,303 new cases detected in 2012, of which 6.7% were children.

Leprosy prevalence in Brazil varies tremendously regionally, with very few cases detected in the southern states (Paraná, Santa Catarina and Rio Grande do Sul) and high new case detection in the central-western regions (Mato Grosso and Goiás), the north (Amazonas, Acre, Rondônia, Tocantins and Pará) and northeast (Maranhão, Piauí, Ceará, Pernambuco and Bahia). Those high-burden states encompass 1,173 municipalities and accounted for 53.5% of all new cases of leprosy in Brazil between 2005 and 2007, although making up just 17% of Brazil’s population.

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Close-up of lesions on shoulder and arm of a child

Dr. Claudio Salgado (Federal University of Pará, Belém) and his survey team of experienced leprosy clinicians, physiotherapists, nurses, phlebotomists, field technicians, IT specialists and laboratory technicians have been performing site visits to over 12 hyperendemic communities in the state of Pará in the Amazon region since 2009. With a population of over 7.5 million, the state historically has had some of the highest annual new case detection rates in the country — over 4.0 per 10,000 population, a rate considered hyperendemic by Brazil’s Ministry of Health. Based on recent surveys, an estimated 40,000 cases will develop in the next decade in Pará alone.

Dr. Salgado’s targeted leprosy surveillance screenings involve clinical and serological examinations of schoolchildren and household contacts of people affected by leprosy. They are funded by grants from the Brazil Ministry of Health, the National Council for Scientific and Technological Development (CNPq), the Pará Amazon Foundation for Research (FAPESPA) and a grant from the Order of Malta for Leprosy Research (MALTALEP), a French organization that funds leprosy research.

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Assessing muscle strength in the hands of a child diagnosed with leprosy on Mosqueiro Island outside of Belém, Pará.

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Homes on the edge of the Amazon River.

For the first survey in 2009, Dr. Salgado’s team consisted of just six people. On a recent screening in the city of Breves on Marajó Island in October 2013, 22 individuals were divided into three teams to maximize the number of schoolchildren and household contacts examined.*

Breves has some of the highest new-case detection rates in the state. Of the 650 schoolchildren and household contacts that we examined in the week we were there, we diagnosed 7% with leprosy — a disturbingly high percentage that is almost 500 times Brazil’s national average of 1.5 new cases per 10,000 population.

Many of the team have been with Dr. Salgado for years, among them Dr. Josafá Barreto, who organizes the surveys. Months before scheduling a visit, he contacts all the schools where we are to perform surveys, making sure that we have permission from the school administrators to visit and providing them with consent forms and information to be distributed to the parents so that they understand what we are doing. He also contacts the local community healthcare agents who have knowledge of people who may have symptoms of leprosy and where they live, as street addresses in some locations are difficult to find without their assistance.

During the week-long surveys, we visit schoolchildren at local schools and household contacts, bleeding and examining between 600 to 1,000 people. The team works up to 14 hours a day or longer, sometimes traveling two hours on rough dirt roads to get to schools and homes in rural areas. For some children, this is the first time they will have seen a doctor in their lives.

The diagnosis of leprosy is based on well-established clinical signs and symptoms. Most of the individuals diagnosed have one or a few hypopigmented anesthetic skin lesions that can be assessed using standard graded monofilament devices to measure the degree of loss of sensation. Areas of skin that have sensory loss on the trunk can be examined for the loss of capacity to produce sweat, another clear indication of nerve damage. Although rare, multibacillary leprosy with symptoms of grade 1 or grade 2 disability can be found, indicating that better surveillance in these areas is necessary to diagnose such cases earlier to prevent lifelong disability.

LEPROSY IN CHILDREN

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Dr. Salgado writes up a prescription for MDT for a child diagnosed with leprosy in Oriximiná, Pará

In a cross-sectional study of 1,592 schoolchildren and household contacts from eight different cities in Pará between 2009 and 2011, we detected 63 new cases, which is a rate of 4%. The average age of those diagnosed with leprosy was 13 years old.

Leprosy in children is correlated with community-level factors, including the recent presence of disease and multiple active foci of transmission in the community. Children that we diagnose with leprosy are selected for follow-up visits during the week to examine their household contacts.

Dwellings may consist of between several to more than 15 occupants, most of whom are related. Frequently if a child is diagnosed, we will often find one or more index cases in the household.

Family members who live with an untreated person can become infected, although it is estimated that it takes between three to seven years after repeated infection for an individual to develop clinical signs and symptoms. This is complicated by the fact that about 90% of individuals worldwide are thought to be naturally immune. In these individuals, a single lesion can spontaneously resolve.

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Nurses at the local school, where MDT is provided free of charge

The reasons why a minority of those infected develop the disease are complicated and may include genetic traits. Other reasons include poor nutrition that can compromise the proper function of a person’s immune system; poverty; living with more than five people in cramped conditions; and poor healthcare delivery in remote areas. (In Pará, only around 40% of the population is covered by the primary health care services.) All these are factors that relate to higher case detection rates.

In many of the cities in Pará where we have done surveys, the number of cases that we detect is much higher than those reported by the healthcare agencies. In one household, we diagnosed five out of six family members with leprosy. This was not only devastating for the family, but also caused great sadness among the doctors and other team members who performed the diagnoses.

In one household, we diagnosed five out of six family members with leprosy.

“In poor communities, like those settled inside the Amazon forest, there exists a very high hidden endemic population that needs special and urgent intervention,” says Dr. Salgado. “Populations living in remote areas in the Amazon region often completely lack medical care, and these are the people who need to be reached, diagnosed and treated.”

BIOMARKERS OF INFECTION

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Visiting the home of a child diagnosed with leprosy to examine household contacts in Oriximiná, Pará

As well as active surveillance for clinical signs of leprosy, we are trying to develop tests to determine biomarkers of infection and disease progression. We have been testing several protein antigens and also the well-known phenolic glycolipid I (PGL-I) antigen. Individuals with a strong positive response to PGL-I, indicating infection with the bacteria causing leprosy, have been found to have an eight-fold higher risk of succumbing to the disease.

We have coupled the use of detecting PGL-I positive responses with a Geographic Information System (GIS) to locate areas of high and low prevalence and identify “hot pockets” within these hyperendemic settings. The WHO has emphasized the use of GIS as one of the tools for leprosy elimination that can “provide a graphical analysis of epidemiological indicators over time, the spatial distribution and severity of the disease, identify pockets of high endemicity and indicate where there is a need to target extra resources.”

We have been able to map index cases and those with the highest anti-PGL-I titers in schoolchildren and household contacts — in other words, those at greatest risk of developing the disease — and are beginning to understand how leprosy is spread from multiple foci of infection in space and time.

One of our main findings is that children with leprosy or those with subclinical infection were in close proximity to spatial and temporal clusters of leprosy cases. These findings can be applied to better guide leprosy control programs to target intervention to these areas more systematically.

This is something we are actively doing and that, over time, should bring down the number of new cases. In the words of Dr. Salgado, “We are confident that targeted examination of children is the key for early diagnosis, preventing disabilities and breaking the chain of transmission.”

AUTHORS:

John S. Spencer, Ph.D. Colorado State University, Fort Collins, CO U.S.A.

Josafá G. Barreto, Ph.D. Federal University of Pará, Belem, Pará, Brazil

Claudio G. Salgado, M.D., Ph.D. Federal University of Pará, Belem, Pará, Brazil

FOOTNOTE

* Two videographers accompanied us and produced a 25-minute video documentary titled “Hanseníase: Endemia Oculta na Floresta Amazônica” (“Leprosy: Hidden Endemic in the Amazon Rain Forest”) with support from the Brazil Ministry of Health. It can be seen on YouTube.