Effectiveness of population-wide screening and mass drug administration for leprosy control in Kiribati: the COMBINE protocol.

INTRODUCTION: Progress towards leprosy elimination is threatened by increasing incidence in 'hot-spot' areas where more effective control strategies are urgently required. In these areas, active case finding and leprosy prevention limited to known contacts is insufficient for control. Population-wide active case-finding together with universal prevention through mass drug administration (MDA) has been shown to be effective in 'hot-spot' areas, but is logistically challenging and expensive. Combining leprosy screening and MDA with other population-wide screening activities such as for tuberculosis may increase programme efficiency. There has been limited evaluation of the feasibility and effectiveness of combined screening and MDA interventions. The COMBINE study aims to bridge this knowledge gap. METHODS AND ANALYSIS: This implementation study will assess the feasibility and effectiveness of active leprosy case-finding and treatment, combined with MDA using either single-dose rifampicin or rifamycin-containing tuberculosis preventive or curative treatment, for reducing leprosy incidence in Kiribati. The leprosy programme will run over 2022-2025 in concert with population-wide tuberculosis screening-and-treatment in South Tarawa. The primary research question is to what extent the intervention reduces the annual leprosy new case detection rate (NCDR) in adults and children compared with routine screening and postexposure prophylaxis (PEP) among close contacts (baseline leprosy control activities). Comparisons will be made with (1) the preintervention NCDR separably among adults and children in South Tarawa (before-after study) and (2) the corresponding NCDRs in the rest of the country. Additionally, the postintervention prevalence of leprosy obtained from a survey of a 'hot-spot' sub-population will be compared with prevalence documented during the intervention. The intervention will be implemented in collaboration with the Kiribati National Leprosy Programme. ETHICS AND DISSEMINATION: Approval has been obtained from the Kiribati Ministry of Health and Medical Services (MHMS), the University of Otago (H22/111) and the University of Sydney (2021/127) Human Research Ethics Committees. Findings will be shared with the MHMS, local communities and internationally through publication.

Population-wide active case finding and prevention for tuberculosis and leprosy elimination in Kiribati: the PEARL study protocol.

INTRODUCTION: Population-wide interventions offer a pathway to tuberculosis (TB) and leprosy elimination, but 'real-world' implementation in a high-burden setting using a combined approach has not been demonstrated. This implementation study aims to demonstrate the feasibility and evaluate the effect of population-wide screening, treatment and prevention on TB and leprosy incidence rates, as well as TB transmission. METHODS AND ANALYSIS: A non-randomised 'screen-and-treat' intervention conducted in the Pacific atoll of South Tarawa, Kiribati. Households are enumerated and all residents ≥3 years, as well as children <3 years with recent household exposure to TB or leprosy, invited for screening. Participants are screened using tuberculin skin testing, signs and symptoms of TB or leprosy, digital chest X-ray with computer-aided detection and sputum testing (Xpert MTB/RIF Ultra). Those diagnosed with disease are referred to the National TB and Leprosy Programme for management. Participants with TB infection are offered TB preventive treatment and those without TB disease or infection, or leprosy, are offered leprosy prophylaxis. The primary study outcome is the difference in the annual TB case notification rate before and after the intervention; a similar outcome is included for leprosy. The effect on TB transmission will be measured by comparing the estimated annual risk of TB infection in primary school children before and after the intervention, as a co-primary outcome used for power calculations. Comparison of TB and leprosy case notification rates in South Tarawa (the intervention group) and the rest of Kiribati (the control group) before, during and after the intervention is a secondary outcome. ETHICS AND DISSEMINATION: Approval was obtained from the University of Sydney Human Research Ethics Committee (project no. 2021/127) and the Kiribati Ministry of Health and Medical Services (MHMS). Findings will be shared with the MHMS and local communities, published in peer-reviewed journals and presented at international conferences.

Evolutionary history of Mycobacterium leprae in the Pacific Islands.

As one of the oldest known human diseases, leprosy or Hansen's disease remains a public health concern around the world with over 200 000 new cases in 2018. Most human leprosy cases are caused by Mycobacterium leprae, but a small number of cases are now known to be caused by Mycobacterium lepromatosis, a sister taxon of M. leprae. The global pattern of genomic variation in M. leprae is not well defined. Particularly, in the Pacific Islands, the origins of leprosy are disputed. Historically, it has been argued that leprosy arrived on the islands during nineteenth century colonialism, but some oral traditions and palaeopathological evidence suggest an older introduction. To address this, as well as investigate patterns of pathogen exchange across the Pacific Islands, we extracted DNA from 39 formalin-fixed paraffin-embedded biopsy blocks dating to 1992-2016. Using whole-genome enrichment and next-generation sequencing, we produced nine M. leprae genomes dating to 1998-2015 and ranging from 4-63× depth of coverage. Phylogenetic analyses indicate that these strains belong to basal lineages within the M. leprae phylogeny, specifically falling in branches 0 and 5. The phylogeographical patterning and evolutionary dating analysis of these strains support a pre-modern introduction of M. leprae into the Pacific Islands. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Hansen's Disease and Complications among Marshallese Persons Residing in Northwest Arkansas, 2003-2017.

Persons from the Republic of the Marshall Islands have among the highest rates of Hansen's disease (HD) in the world; the largest Marshallese community in the continental United States is in northwest Arkansas. In 2017, the HD Ambulatory Care Clinic in Springdale, Arkansas, informed the Arkansas Department of Health (ADH) that Marshallese persons with HD had severe disease with frequent complications. To characterize their illness, we reviewed ADH surveillance reports of HD among Marshallese persons in Arkansas treated during 2003-2017 (n = 42). Hansen's Disease prevalence among Marshallese in Arkansas (11.7/10,000) was greater than that in the general U.S. population. Complications included arthritis (38%), erythema nodosum leprosum (21%), and prolonged treatment lasting > 2 years (40%). The majority (82%) of patients treated for > 2 years had documented intermittent therapy. Culturally appropriate support for therapy and adherence is needed in Arkansas.

Surveillance of Leprosy in Kiribati, 1935-2017.

In Kiribati, unlike most countries, high and increasing numbers of cases of leprosy have been reported despite the availability of multidrug therapy and efforts to improve case finding and management. Historic records show that 28 cases had been identified by 1925. A systematic population survey in 1997 identified 135 new cases; the mean incidence rate for 1993-1997 was 7.4/10,000 population. After administering mass chemoprophylaxis, the country reached the elimination threshold (prevalence <1/10,000), but case numbers have rebounded. The mean annualized rate of new cases in 2013-2017 was 15/10,000 population, with the highest new case rates (>20/10,000 population) in the main population centers of South Tarawa and Betio. Spread is expected to continue in areas where crowding and poor socioeconomic conditions persist and may accelerate as sea levels rise from climate change. New initiatives to improve social conditions are needed, and efforts such as postexposure chemoprophylaxis should be implemented to prevent spread.

Case report: Hansen's disease in an active duty soldier presenting with type 1 reversal reaction.

Leprosy, or Hansen's disease (HD), is caused by the bacterium Mycobacterium leprae and is a significant cause of morbidity worldwide. Clinical manifestations range from isolated skin rash to severe peripheral neuropathy. Treatment involves a prolonged course of multiple antimicrobials. Although rare in the U.S., with only 168 new cases reported in 2016, HD remains a prevalent disease throughout the world, with 214,783 new cases worldwide that same year.1 It remains clinically relevant for service members born in and deployed to endemic regions. This report describes a case of HD diagnosed in an active duty soldier born and raised in Micronesia, a highly endemic region.

Predicting the impact of household contact and mass chemoprophylaxis on future new leprosy cases in South Tarawa, Kiribati: A modelling study.

BACKGROUND: The country of Kiribati is a small Pacific island nation which had a new case detection rate of 191 per 100,000 in 2016, and is one of the few countries yet to reach the WHO leprosy elimination goal. Chemoprophylaxis of household contacts of new cases, or to the whole population in a highly endemic areas have been found to be effective in reducing new case rates. This study investigated the potential impact of different chemoprophylaxis strategies on future cases in South Tarawa, the main population centre of Kiribati. METHODOLOGY: The microsimulation model SIMCOLEP was calibrated to simulate the South Tarawa population and past leprosy control activities, and replicate annual new cases from 1989 to 2016. The impact of six different strategies for delivering one round of single dose rifampicin (SDR) chemoprophylaxis to household contacts of new cases and/or one or three rounds of SDR to the whole population was modelled from 2017 to 2030. PRINCIPAL FINDINGS: Our model predicted that continuing the existing control program of high levels of public awareness, passive case detection, and treatment with multidrug treatment would lead to a substantial reduction in cases but this was less effective than all modelled intervention scenarios. Mass chemoprophylaxis led to a faster initial decline in cases than household contact chemoprophylaxis alone, however the decline under the latter was sustained for longer. The greatest cumulative impact was for household contact chemoprophylaxis with three rounds of mass chemoprophylaxis at one-year intervals. CONCLUSIONS: The results suggest that control of leprosy would be achieved most rapidly with a combination of intensive population-based and household chemoprophylaxis. These findings may be generalisable to other countries where crowding places social contacts as well as household contacts of cases at risk of developing leprosy.

Delayed Diagnosis of Leprosy in a Micronesian Soldier - Case Report.

Lepromatous leprosy represents a cutaneous infection by the bacterium Mycobacterium leprae. Once considered a common, fatal disease, leprosy has become increasingly rare with modern, inexpensive antibiotics. Most healthcare workers will never encounter a case of leprosy due to the low prevalence of the disease. However, military physicians, through deployments and contact with foreign-born servicemembers, are one of the first lines of defense against this disease. With an unknown method of transmission and an insidiously slow replication, it can take years for the disease to fully manifest. There are multiple cutaneous manifestations associated with the infection that can mimic other infectious etiologies, stalling appropriate diagnosis and treatment. To determine which treatment course is recommended requires evaluation of disease dissemination and the level of host immune response. As the incidence of reported leprosy cases continues to decline, disease education on diagnosis and treatment is imperative to enhance early detection and intervention. Understanding the populations at risk for leprosy and its insidious presentation will aid the practitioner in minimizing disease burden for both U.S. servicemembers and our foreign partners.

Leprosy in a Midwestern Dermatology Clinic: Report of 9 Patients.

OBJECTIVE: To describe the clinical features and epidemiology of leprosy in patients evaluated in a Midwestern dermatology clinic. PATIENTS AND METHODS: We performed a retrospective review of clinical and laboratory data from patients with leprosy who were evaluated in the Department of Dermatology at Mayo Clinic in Rochester, Minnesota, from January 1, 1994, through December 31, 2017. RESULTS: Nine patients, 7 male and 2 female, were identified, ranging in age from 15 to 63 years (mean age, 38 years). Six of the 9 patients (67%) were foreign-born: 3 from Oceania (2 from Micronesia and 1 from Guam), 1 from Southeast Asia (Indonesia), and 2 from Mexico. Three patients were born in the United States. All 9 patients presented with skin lesions (granulomatous histopathologic type), and 8 had neuropathy. Leprosy was multibacillary in 8 patients and paucibacillary in 1. Two patients experienced a type 1 treatment reaction, and 5 had type 2 reactions. Three of the 9 patients had speciation by polymerase chain reaction (Mycobacterium leprae in 2 and Mycobacterium lepromatosis in 1). CONCLUSION: Despite its rarity in the United States, leprosy should be considered in the differential diagnosis when evaluating both foreign- and US-born patients with granulomatous dermatitis and peripheral neuropathy. Because M lepromatosis was not identified until 2008 and requires polymerase chain reaction for diagnosis, the incidence of this species among patients with leprosy diagnosed in earlier years is unknown.

Marshallese COFA Migrants in Arkansas.

Arkansas is home to one of the largest populations of Marshallese in the world. Marshallese communities suffer from a disproportionate incidence of chronic diseases, including obesity, cardiovascular disease, diabetes, and infectious diseases, such as Hansen's disease (leprosy), tuberculosis, and types of hepatitis. There are a number of structural, legal, economic, and social issues that must be addressed in order to reduce health disparities and increase access to health care for Marshallese living in Arkansas.

Characteristics of a dengue outbreak in a remote pacific island chain--Republic of The Marshall Islands, 2011-2012.

Dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (DENV-1-4). Although dengue outbreaks regularly occur in many regions of the Pacific, little is known about dengue in the Republic of the Marshall Islands (RMI). To better understand dengue in RMI, we investigated an explosive outbreak that began in October 2011. Suspected cases were reported to the Ministry of Health, serum specimens were tested with a dengue rapid diagnostic test (RDT), and confirmatory testing was performed using RT-PCR and IgM ELISA. Laboratory-positive cases were defined by detection of DENV nonstructural protein 1 by RDT, DENV nucleic acid by RT-PCR, or anti-DENV IgM antibody by RDT or ELISA. Secondary infection was defined by detection of anti-DENV IgG antibody by ELISA in a laboratory-positive acute specimen. During the four months of the outbreak, 1,603 suspected dengue cases (3% of the RMI population) were reported. Of 867 (54%) laboratory-positive cases, 209 (24%) had dengue with warning signs, six (0.7%) had severe dengue, and none died. Dengue incidence was highest in residents of Majuro and individuals aged 10-29 years, and ∼95% of dengue cases were experiencing secondary infection. Only DENV-4 was detected by RT-PCR, which phylogenetic analysis demonstrated was most closely related to a virus previously identified in Southeast Asia. Cases of vertical DENV transmission, and DENV/Salmonella Typhi and DENV/Mycobacterium leprae co-infection were identified. Entomological surveys implicated water storage containers and discarded tires as the most important development sites for Aedes aegypti and Ae. albopictus, respectively. Although this is the first documented dengue outbreak in RMI, the age groups of cases and high prevalence of secondary infection demonstrate prior DENV circulation. Dengue surveillance should continue to be strengthened in RMI and throughout the Pacific to identify and rapidly respond to future outbreaks.

Health concerns of Micronesian peoples.

Several states in the United States have been experiencing an influx of migrants from an area of the world that most people have only heard of when learning about the atomic bomb and World War II. This area is the former U.S. Trust Territory of Pacific Islands now called the Freely Associated States. At the end of World War II, the United States took possession of many of these islands and in 1948, the United States formally took over administration of the Marshalls, the Carolines, Palau, and the Northern Marianas islands. Collectively this area is known as Micronesia. Micronesians come from areas that have high prevalence of several communicable diseases and there is growing concern that Micronesian immigrants may enable the spread of infectious disease to the United States from Asia. Data concerning Hansen's disease and tuberculosis support this claim. According to data from the Hawai'i State Department of Health, a 5-year trend examining new cases of tuberculosis in Hawai'i identified that 65 out of 77 new cases came from the Freely Associated States of Micronesia. Presented is an overview of the health concerns and health status of the people from the Federated States of Micronesia.

Hansen disease among Micronesian and Marshallese persons living in the United States.

An increasing proportion of Hansen disease cases in the United States occurs among migrants from the Micronesian region, where leprosy prevalence is high. We abstracted surveillance and clinical records of the National Hansen's Disease Program to determine geographic, demographic, and clinical patterns. Since 2004, 13% of US cases have occurred in this migrant population. Although Hawaii reported the most cases, reports have increased in the central and southern states. Multibacillary disease in men predominates on the US mainland. Of 49 patients for whom clinical data were available, 37 (75%) had leprosy reaction, neuropathy, or other complications; 17 (37%) of 46 completed treatment. Comparison of data from the US mainland with Hawaii and country-of-origin suggests under-detection of cases in pediatric and female patients and with paucibacillary disease in the United States. Increased case finding and management, and avoidance of leprosy-labeled stigma, is needed for this population.

Role of GIS technology during leprosy elimination efforts in Pohnpei.

This article summarizes Pohnpei State Department of Health Services' utilization of GIS technology and GPS mapping of leprosy cases during the leprosy elimination efforts. Maps generated from ArcMap provided 'hotspots' or areas of high case density, thus providing for more focused screening. Introducing GIS technology in the elimination efforts has led to a diminution of the target number of screened clients per year, thus minimizing resource utilization. GPS technology as a health planning tool in small Pacific island countries can synergize local screening efforts and improve overall public health planning and implementation, in a way that is cost-effective and resource friendly.

Leprosy: a case series and review.

Hansen disease, historically known as leprosy, is caused by Mycobacterium leprae. The disease is rare in the United States but remains endemic among certain immigrant populations, and may manifest years after infection. The US military has a number of active duty troops originally from endemic countries. Recently, three US soldiers with Hansen disease were evaluated at Walter Reed Army Medical Center. The mean time to diagnosis was 8 months (range, 2 to 18 months). All three patients were initially misdiagnosed and treated for other skin infections or contact dermatitis. These cases illustrate the importance of prompt recognition and treatment of Hansen disease to prevent permanent disability and disfigurement. The clinical presentation, diagnosis, classification, and currently recommended therapeutic regimens for Hansen disease are discussed.

Lepromatous leprosy and reversal reaction in a Micronesian immigrant.

A 25-year-old Micronesian man from the island of Otia developed erythematous plaques on his legs. He was diagnosed with erythema nodosum and treated with systemic prednisone. Two months later, he presented with erythematous nodules on his forehead, cheeks, and chin (Fig. 1). Examination revealed scattered violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple macules on his palms and soles. Laboratory evaluation included negative serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis A, B, and C. Routine histopathology revealed nodular aggregates of histiocytes, plasma cells, and lymphocytes. Histiocytes showed basophilic clusters of organisms within vacuoles, suggesting globi. Acid-fast stain revealed numerous acid-fast-positive rod-shaped organisms. The bacterial index on the Fite stain was four (bacterial index/Ridley's logarithmic scale, indicating 10-100 bacteria/high power field) (Fig. 2). An acid-fast stain obtained from a smear of tissue was positive for acid-fast bacilli, but no acid-fast bacilli were cultured. After the first day of treatment with dapsone 100 mg, rifampin 600 mg, and clofazimine 50 mg, the patient complained of burning and pain in his ankles and wrists. There was intense erythema within the lesions. Edema developed in his hands and feet. Consultation with the Gillis W. Long Hansen's Disease Center in Carville, Louisiana, recommended prompt treatment with corticosteroids. The edema of the hands and wrists was treated as a type I reversal reaction with prednisone 1 mg/kg/day. Subsequently, the edema and neuralgia quickly resolved in his distal extremities.

Leprosy chemoprophylaxis in Micronesia.

A programme of chemoprophylaxis was introduced as a component of the leprosy control programme in the Federated States of Micronesia (FSM), beginning in 1996. The entire population of the country was to be screened, and a single dose of 600 mg rifampicin, 400 mg ofloxacin and 100 mg minocycline (ROM) was to be administered to the entire population. Two rounds of screening the entire population were carried out, approximately 1 year apart, and chemoprophylaxis was administered at the time of each screening. Ninety percent of the population were screened at least once, and 55% were screened in both rounds; 87% of the population received at least one dose, and 54% received two doses. In the course of the first round, 322 new cases were detected, whereas only 80 new cases were detected during the second round, of whom only 12 had received chemoprophylaxis in the course of the first round. A third round of screening, confined to a small number of villages in both Chuuk and Pohnpei, in which states leprosy endemicity was high, was carried out approximately 2 years after the second. Only 16 new cases were detected during the third round of screening, whereas 102 new cases had been detected in this same population during the first round of screening, and 32 new cases during the second. Six of the 16 newly detected cases stated that they had been administered chemoprophylaxis at least once; however, this information may not be reliable.

Cluster of leprosy cases in Kona, Hawaii; impact of the Compact of Free Association.

International travel and migration will continue to contribute to the changing patterns of Hansen's disease (HD) in the United States. The majority of cases will be immigrants and refugees entering the country from leprosy-endemic regions. The Compact of Free Association, through its provision of free travel between the Freely Associated States and the United States without need for health screening, has created new public health issues. This cluster of HD cases in Kona, Hawaii, U.S.A., highlights the difficulties in detecting and monitoring the spread of disease in immigrant populations. This is a growing problem only likely to worsen in the coming years. In groups with cultural, language or other socioeconomic barriers, special and creative methods may be needed to tackle the problems of detection, treatment and education. Clinicians must remain mindful of the diagnosis of HD in high-risk groups.