RESUMO
WHO and its partners aim to interrupt yaws transmission in countries of endemicity and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6 to 15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semiquantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.
Assuntos
Azitromicina , Bouba , Formação de Anticorpos , Azitromicina/uso terapêutico , Criança , Gana , Humanos , Papua Nova Guiné , Treponema pallidum , Bouba/tratamento farmacológicoRESUMO
Yaws, a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue, manifests as ulcerative skin lesions. Nucleic acid amplification tests, like loop-mediated isothermal amplification (LAMP), are versatile tools to distinguish yaws from infections that cause similar skin lesions, primarily Haemophilus ducreyi. We developed a novel molecular test to simultaneously detect T. pallidum and H. ducreyi based on mediator displacement LAMP. We validated the T. pallidum and H. ducreyi LAMP (TPHD-LAMP) by testing 293 clinical samples from patients with yaws-like lesions. Compared with quantitative PCR, the TPHD-LAMP demonstrated high sensitivity and specificity for T. pallidum (84.7% sensitivity, 95.7% specificity) and H. ducreyi (91.6% sensitivity, 84.8% specificity). This novel assay provided rapid molecular confirmation of T. pallidum and H. ducreyi DNA and might be suitable for use at the point of care. TPHD-LAMP could support yaws eradication by improving access to molecular diagnostic tests at the district hospital level.
Assuntos
Cancroide/diagnóstico , Haemophilus ducreyi/isolamento & purificação , Treponema pallidum/isolamento & purificação , Bouba/diagnóstico , Cancroide/microbiologia , Criança , Feminino , Gana , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Papua Nova Guiné , Sensibilidade e Especificidade , Bouba/microbiologiaRESUMO
BACKGROUND: Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication. METHODS: Between April 15, 2013, and Oct 24, 2016, we did a longitudinal study on a Papua New Guinea island (Lihir; 16â092 population) in which yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued every 6 months for 42 months. We used genotyping and travel history to identify importation events. Active yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator. The study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programmes reduced the prevalence of active yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline -1·7%, 95% CI, -1·9 to -1·4; p<0·0001), but the infection began to re-emerge after 24 months with a significant increase to 0·4% at 42 months (difference from 18 months 0·3%, 95% CI 0·1 to 0·4; p<0·0001). At each timepoint after baseline, more than 70% of the total community burden of yaws was found in individuals who had not had the mass treatment or as new infections in non-travelling residents. At months 36 and 42, five cases of active yaws, all from the same village, showed clinical failure following azithromycin treatment, with PCR-detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin. A sustained decrease in the prevalence of high-titre latent yaws from 13·7% to <1·5% in asymptomatic children aged 1-5 years old and of genetic diversity of yaws strains from 0·139 to less than 0·046 between months 24 and 42 indicated a reduction in transmission of infection. INTERPRETATION: The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to the individuals who were absent at the time of mass treatment in whom yaws reactivated; repeated mass treatment might be necessary to eliminate yaws. To our knowledge, this is the first report of the emergence of azithromycin-resistant T p pertenue and spread within one village. Communities' surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance. FUNDING: ISDIN laboratories, Newcrest Mining Limited, and US Public Health Service National Institutes of Health.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Administração Massiva de Medicamentos , Bouba/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Erradicação de Doenças , Farmacorresistência Bacteriana/genética , Feminino , Variação Genética , Humanos , Lactente , Estudos Longitudinais , Masculino , Papua Nova Guiné/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , RNA Ribossômico 23S/genética , Resultado do Tratamento , Treponema pallidum/genética , Bouba/epidemiologia , Bouba/prevenção & controleRESUMO
BACKGROUND: Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. METHODS: We performed repeated clinical surveys for active yaws, serologic surveys for latent yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious yaws in the entire population and the prevalence of latent yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. RESULTS: At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P<0.001). The prevalence of high-titer latent yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P<0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen. CONCLUSIONS: The prevalence of active and latent yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of yaws. Our results support the WHO strategy for the eradication of yaws. (Funded by Newcrest Mining and International SOS; YESA-13 ClinicalTrials.gov number, NCT01955252.).
Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Treponema pallidum/isolamento & purificação , Bouba/tratamento farmacológico , Adolescente , Adulto , Distribuição por Idade , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Cancroide/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana/genética , Doenças Endêmicas , Haemophilus ducreyi/isolamento & purificação , Humanos , Lactente , Papua Nova Guiné/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Treponema pallidum/genética , Bouba/diagnóstico , Bouba/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU. METHODS: We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment. RESULTS: We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group, and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR. CONCLUSIONS: Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Haemophilus ducreyi/efeitos dos fármacos , Úlcera Cutânea/tratamento farmacológico , Administração Oral , Adolescente , Azitromicina/efeitos adversos , Cancroide/epidemiologia , Cancroide/microbiologia , Criança , Estudos de Coortes , Feminino , Haemophilus ducreyi/genética , Humanos , Masculino , Papua Nova Guiné/epidemiologia , Reação em Cadeia da Polimerase , Saúde Pública , Estudos Retrospectivos , Úlcera Cutânea/microbiologia , Resultado do Tratamento , Treponema pallidum/genética , Treponema pallidum/isolamento & purificaçãoRESUMO
BACKGROUND: The objective of the study was to describe an m-health initiative to strengthen malaria surveillance in a 184-health facility, multi-province, project aimed at strengthening the National Health Information System (NHIS) in a country with fragmented malaria surveillance, striving towards enhanced control, pre-elimination. METHODS: A remote-loading mobile application and secure online platform for health professionals was created to interface with the new system (eNHIS). A case-based malaria testing register was developed and integrated geo-coded households, villages and health facilities. A malaria programme management dashboard was created, with village-level malaria mapping tools, and statistical algorithms to identify malaria outbreaks. RESULTS: Since its inception in 2015, 160,750 malaria testing records, including village of residence, have been reported to the eNHIS. These case-based, geo-coded malaria data are 100% complete, with a median data entry delay of 9 days from the date of testing. The system maps malaria to the village level in near real-time as well as the availability of treatment and diagnostics to health facility level. Data aggregation, analysis, outbreak detection, and reporting are automated. CONCLUSIONS: The study demonstrates that using mobile technologies and GIS in the capture and reporting of NHIS data in Papua New Guinea provides timely, high quality, geo-coded, case-based malaria data required for malaria elimination. The health systems strengthening approach of integrating malaria information management into the eNHIS optimizes sustainability and provides enormous flexibility to cater for future malaria programme needs.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Sistemas de Informação em Saúde/normas , Malária/epidemiologia , Malária/prevenção & controle , Algoritmos , Surtos de Doenças/prevenção & controle , Sistemas de Informação Geográfica , Humanos , Aplicativos Móveis , Papua Nova Guiné/epidemiologia , Projetos PilotoRESUMO
BACKGROUND: Cholera continues to be a devastating disease in many developing countries where inadequate safe water supply and poor sanitation facilitate spread. From July 2009 until late 2011 Papua New Guinea experienced the first outbreak of cholera recorded in the country, resulting in >15,500 cases and >500 deaths. METHODS: Using the national cholera database, we analysed the spatio-temporal distribution and clustering of the Papua New Guinea cholera outbreak. The Kulldorff space-time permutation scan statistic, contained in the software package SatScan v9.2 was used to describe the first 8 weeks of the outbreak in Morobe Province before cholera cases spread throughout other regions of the country. Data were aggregated at the provincial level to describe the spread of the disease to other affected provinces. RESULTS: Spatio-temporal and cluster analyses revealed that the outbreak was characterized by three distinct phases punctuated by explosive propagation of cases when the outbreak spread to a new region. The lack of road networks across most of Papua New Guinea is likely to have had a major influence on the slow spread of the disease during this outbreak. CONCLUSIONS: Identification of high risk areas and the likely mode of spread can guide government health authorities to formulate public health strategies to mitigate the spread of the disease through education campaigns, vaccination, increased surveillance in targeted areas and interventions to improve water, sanitation and hygiene.
Assuntos
Cólera/epidemiologia , Surtos de Doenças , Adolescente , Adulto , Criança , Pré-Escolar , Análise por Conglomerados , Controle de Doenças Transmissíveis , Países em Desenvolvimento , Feminino , Geografia , Humanos , Higiene , Lactente , Masculino , Pessoa de Meia-Idade , Papua Nova Guiné/epidemiologia , Saúde Pública , Análise Espaço-Temporal , Vacinação , Microbiologia da Água , Abastecimento de Água , Adulto JovemRESUMO
The health care system in Papua New Guinea is fragile, and surveillance systems infrequently meet international standards. To strengthen outbreak identification, health authorities piloted a mobile phone-based syndromic surveillance system and used established frameworks to evaluate whether the system was meeting objectives. Stakeholder experience was investigated by using standardized questionnaires and focus groups. Nine sites reported data that included 7 outbreaks and 92 cases of acute watery diarrhea. The new system was more timely (2.4 vs. 84 days), complete (70% vs. 40%), and sensitive (95% vs. 26%) than existing systems. The system was simple, stable, useful, and acceptable; however, feedback and subnational involvement were weak. A simple syndromic surveillance system implemented in a fragile state enabled more timely, complete, and sensitive data reporting for disease risk assessment. Feedback and provincial involvement require improvement. Use of mobile phone technology might improve the timeliness and efficiency of public health surveillance.
Assuntos
Telefone Celular , Vigilância em Saúde Pública/métodos , Análise Custo-Benefício , Notificação de Doenças , Humanos , Papua Nova Guiné , Pesquisa Qualitativa , Controle de Qualidade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua New Guinea. METHODS: This open-label, cluster-randomised study was done in 24 villages in a district endemic for lymphatic filariasis in Papua New Guinea. Villages paired by population size were randomly assigned to receive mass drug administration with a single dose of the triple-drug oral regimen of ivermectin (200 µg per kg of bodyweight) plus diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg) or a single dose of the two-drug oral regimen of diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg). This is a follow-on study of a previously reported safety study (ClinicalTrials.govNCT02899936). All residents aged 5 years or older and non-pregnant women were asked to participate. After cross-sectional night blood microfilariae and circulating filarial antigen surveys, mass drug administration was provided at baseline and repeated 12 months later. The primary outcomes were mean prevalence of microfilariae and circulating filarial antigen at 12 months and 24 months, assessed in all residents willing to participate at each timepoint. This study is registered with ClinicalTrials.gov, NCT03352206. FINDINGS: Between Nov 18, 2016, and May 26, 2017, 4563 individuals were enrolled in 24 clusters; 12 clusters (2382 participants) were assigned to the triple-drug regimen and 12 clusters (2181 participants) to the two-drug regimen. Mean drug ingestion rates (of residents aged ≥5 years) were 66·1% at baseline and 63·2% at 12 months in communities assigned to the triple-drug regimen and 65·9% at baseline and 54·9% at 12 months in communities assigned to the two-drug regimen. Microfilariae prevalence in the triple-drug regimen group decreased from 105 (4·4%) of 2382 participants (95% CI 3·6-5·3) at baseline to nine (0·4%) of 2319 (0·1-0·7) at 12 months and four (0·2%) of 2086 (0·1-0·5) at 24 months. In the two-drug regimen group, microfilariae prevalence decreased from 93 (4·3%) of 2181 participants (95% CI 3·5-5·2) at baseline to 29 (1·5%) of 1963 (1·0-2·1) at 12 months and eight (0·4%) of 1844 (0·2-0·9) at 24 months (adjusted estimated risk ratio 4·5, 95% CI 1·4-13·8, p=0·0087, at 12 months; 2·9, 95% CI 1·0-8·8, p=0·058, at 24 months). The prevalence of circulating filarial antigen decreased from 523 (22·0%) of 2382 participants (95% CI 20·3-23·6) at baseline to 378 (16·3%) of 2319 (14·9-17·9) at 12 months and 156 (7·5%) of 2086 (6·4-8·7) at 24 months in the triple-drug regimen group and from 489 (22·6%) of 2168 participants (20·7-24·2) at baseline to 358 (18·2%) of 1963 (16·7-20·1) at 12 months and 184 (10·0%) of 1840 (8·7-11·5) at 24 months in the two-drug regimen group; after adjustment, differences between groups were not significant. INTERPRETATION: Mass administration of the triple-drug regimen was more effective than the two-drug regimen in reducing microfilariae prevalence in communities to less than the target level of 1%, but did not reduce circulating filarial antigen prevalence to less than 2%. These results support the use of mass drug administration with the triple-drug regimen to accelerate elimination of lymphatic filariasis. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Filariose Linfática , Filaricidas , Albendazol/uso terapêutico , Estudos Transversais , Dietilcarbamazina/uso terapêutico , Quimioterapia Combinada , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Feminino , Filaricidas/uso terapêutico , Humanos , Ivermectina/uso terapêutico , Administração Massiva de Medicamentos , Papua Nova Guiné/epidemiologiaRESUMO
BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. PRINCIPAL FINDINGS: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). CONCLUSION: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. TRIAL REGISTRATION: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.
Assuntos
Albendazol/administração & dosagem , Dietilcarbamazina/administração & dosagem , Filariose Linfática/tratamento farmacológico , Filaricidas/administração & dosagem , Ivermectina/administração & dosagem , Adolescente , Adulto , Idoso , Albendazol/efeitos adversos , Animais , Criança , Pré-Escolar , Dietilcarbamazina/efeitos adversos , Quimioterapia Combinada , Filariose Linfática/parasitologia , Feminino , Humanos , Ivermectina/efeitos adversos , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Papua Nova Guiné , Resultado do Tratamento , Wuchereria bancrofti/efeitos dos fármacos , Wuchereria bancrofti/fisiologia , Adulto JovemRESUMO
Papua New Guinea (PNG) faces a critical shortage of human resources to address pressing public health challenges arising from an increasing burden of communicable and non-communicable diseases. PNG is an independent State in the Pacific and home to 8.2 million people. Resource and infrastructure constraints due to the country's challenging geography have made it difficult and expensive to deliver health services and implement health programmes. The National Department of Health and its partners developed a field epidemiology training programme of Papua New Guinea (FETPNG) to strengthen the country's public health workforce. The training programme covers field epidemiology competencies and includes the design, implementation and evaluation of evidence-based interventions by Fellows. From 2013 to 2018, FETPNG graduated 81 field epidemiologists. Most FETPNG graduates (84%) were from provincial or district health departments or organisations. Many of their intervention projects resulted in successful public health outcomes with tangible local impacts. Health challenges addressed included reducing the burden of multi-drug resistant-tuberculosis (TB), increasing immunisation coverage, screening and treating HIV/TB patients, and improving reproductive health outcomes. FETPNG Fellows and graduates have also evaluated disease surveillance systems and investigated disease outbreaks. Early and unwavering national ownership of FETPNG created a sustainable programme fitting the needs of this low-resource country. A focus on designing and implementing effective public health interventions not only provides useful skills to Fellows but also contributes to real-time, tangible and meaningful improvements in the health of the population. The graduates of FETPNG now provide a critical mass of public health practitioners across the country. Their skills in responding to outbreaks and public health emergencies, in collecting, analysing and interpreting data, and in designing, implementing and evaluating public health interventions continues to advance public health in PNG.
RESUMO
BACKGROUND: A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws. METHODS: We did a non-inferiority, open-label, randomised controlled trial in children aged 6-15 years who were recruited from schools in Ghana and schools and the community in Papua New Guinea. Participants were enrolled based on the presence of a clinical lesion that was consistent with infectious primary or secondary yaws and a positive rapid diagnostic test for treponemal and non-treponemal antibodies. Participants were randomly assigned (1:1) to receive either standard-dose (30 mg/kg) or low-dose (20 mg/kg) azithromycin by a computer-generated random number sequence. Health-care workers assessing clinical outcomes in the field were not blinded to the patient's treatment, but investigators involved in statistical or laboratory analyses and the participants were blinded to treatment group. We followed up participants at 4 weeks and 6 months. The primary outcome was cure at 6 months, defined as lesion healing at 4 weeks in patients with active yaws and at least a four-fold decrease in rapid plasma reagin titre from baseline to 6 months in patients with active and latent yaws. Active yaws was defined as a skin lesion that was positive for Treponema pallidum ssp pertenue in PCR testing. We used a non-inferiority margin of 10%. This trial was registered with ClinicalTrials.gov, number NCT02344628. FINDINGS: Between June 12, 2015, and July 2, 2016, 583 (65·1%) of 895 children screened were enrolled; 292 patients were assigned a low dose of azithromycin and 291 patients were assigned a standard dose of azithromycin. 191 participants had active yaws and 392 had presumed latent yaws. Complete follow-up to 6 months was available for 157 (82·2%) of 191 patients with active yaws. In cases of active yaws, cure was achieved in 61 (80·3%) of 76 patients in the low-dose group and in 68 (84·0%) of 81 patients in the standard-dose group (difference 3·7%; 95% CI -8·4 to 15·7%; this result did not meet the non-inferiority criterion). There were no serious adverse events reported in response to treatment in either group. The most commonly reported adverse event at 4 weeks was gastrointestinal upset, with eight (2·7%) participants in each group reporting this symptom. INTERPRETATION: In this study, low-dose azithromycin did not meet the prespecified non-inferiority margin compared with standard-dose azithromycin in achieving clinical and serological cure in PCR-confirmed active yaws. Only a single participant (with presumed latent yaws) had definitive serological failure. This work suggests that 20 mg/kg of azithromycin is probably effective against yaws, but further data are needed. FUNDING: Coalition for Operational Research on Neglected Tropical Diseases.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Bouba/tratamento farmacológico , Adolescente , Criança , Relação Dose-Resposta a Droga , Feminino , Gana , Humanos , Masculino , Papua Nova Guiné , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. METHODS: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2·0%, 95% CI -8·3 to 4·3), meeting the prespecified criteria for non-inferiority. INTERPRETATION: On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. FUNDING: Newcrest Mining Limited and ISDIN laboratories.
Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Bouba/tratamento farmacológico , Bouba/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Papua Nova Guiné/epidemiologia , Reação em Cadeia da Polimerase , Treponema pallidum/isolamento & purificação , Bouba/transmissãoRESUMO
BACKGROUND: To eradicate yaws, national control programmes use the Morges strategy (initial mass treatment and biannual resurveys). The resurvey component is designed to actively detect and treat remaining yaws cases and is initiated on the basis of laboratory-supported reactive non-treponemal serology (using the rapid plasma reagin [RPR] test). Unfortunately, the RPR test is available rarely in yaws-endemic areas. We sought to assess a new point-of-care assay-the Dual Path Platform (DPP) syphilis assay, which is based on simultaneous detection of antibodies to treponemal and non-treponemal antigens-for guiding use of antibiotics for yaws eradication. A secondary goal was to ascertain at what timepoint the DPP assay line reverted to negative after treatment. METHODS: 703 children (aged 1-18 years) with suspected clinical yaws living in two remote, yaws-endemic villages in Papua New Guinea were enrolled. Clinical suspicion of yaws was established according to a WHO pictorial guide. We obtained blood samples from all patients. We calculated the sensitivity and specificity of the DPP assay for detection of antibodies to treponemal (T1) and non-treponemal (T2) antigens and compared values against those obtained with standard laboratory tests (the Treponema pallidum haemagglutination assay [TPHA] and the RPR test). We followed up a subsample of children with dually positive serology (T1 and T2) to monitor changes in DPP optical density (using an automatic reader) at 3 and 6 months. This trial is registered with ClinicalTrials.gov, number NCT01841203. FINDINGS: Of 703 participants, 389 (55%) were reactive for TPHA, 305 (43%) for the RPR test, and 287 (41%) for both TPHA and the RPR test. The DPP T1 (treponemal) assay had a sensitivity of 88·4% (95% CI 84·8-91·4) and specificity of 95·2% (92·2-97·3). The DPP T2 (non-treponemal) assay had a sensitivity of 87·9% (83·7-91·3) and specificity of 92·5% (89·4-94·9). In subgroup analyses, sensitivities and specificities did not differ according to type of specimen (plasma vs whole blood). For specimens with an RPR titre of 1:8 or greater, the sensitivity of the DPP T2 assay was 94·1% (95% CI 89·9-96·9). Serological cure (including seroreversion or a fourfold reduction in optical density value) was attained at 6 months in 173 (95%) of 182 children with dual-positive serology. INTERPRETATION: The DPP assay is accurate for identification of antibodies to treponemal and non-treponemal antigens in patients with yaws and avoids the need for laboratory support. A change of diagnostic procedure from the currently implemented RPR test to the simpler DPP assay could ease the implementation of yaws eradication activities. FUNDING: Chembio Diagnostic Systems, Newcrest Mining, and the Papua New Guinea National Department of Health.
Assuntos
Anticorpos Antibacterianos/sangue , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos , Sorodiagnóstico da Sífilis/métodos , Bouba/sangue , Bouba/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Papua Nova Guiné , Sensibilidade e Especificidade , Sífilis/sangue , Sífilis/diagnósticoRESUMO
ISSUE: Papua New Guinea is striving to achieve the minimum core requirements under the International Health Regulations in surveillance and outbreak response, and has experienced challenges in the availability and distribution of health professionals. CONTEXT: Since mid-2009, a large cholera outbreak spread across lowland regions of the country and has been associated with more than 15 500 notifications at a case fatality ratio of 3.2%. The outbreak placed significant pressure on clinical and public health services. ACTION: We describe some of the challenges to cholera preparedness and response in this human resource-limited setting, the strategies used to ensure effective cholera management and lessons learnt. OUTCOME: Cholera task forces were useful to establish a clear system of leadership and accountability for cholera outbreak response and ensure efficiencies in each technical area. Cholera outbreak preparedness and response was strongest when human resource and health systems functioned well before the outbreak. Communication relied on coordination of existing networks and methods for empowering local leaders and villagers to modify behaviours of the population. DISCUSSION: In line with the national health emergencies plan, the successes of human resource strategies during the cholera outbreak should be built upon through emergency exercises, especially in non-affected provinces. Population needs for all public health professionals involved in health emergency preparedness and response should be mapped, and planning should be implemented to increase the numbers in relevant areas. Human resource planning should be integrated with health emergency planning. It is essential to maintain and strengthen the human resource capacities and experiences gained during the cholera outbreak to ensure a more effective response to the next health emergency.
Assuntos
Cólera/epidemiologia , Cólera/terapia , Surtos de Doenças/estatística & dados numéricos , Planejamento em Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Controle de Doenças Transmissíveis/organização & administração , Serviços de Saúde Comunitária/organização & administração , Humanos , Papua Nova Guiné/epidemiologia , Estudos RetrospectivosRESUMO
@#Objective: Routine immunization coverage in Papua New Guinea has decreased in the past 5 years. This persistently low routine immunization coverage has resulted in low population immunity and frequent outbreaks of vaccine-preventable disease across the country. We describe the use of a catch-up programme to improve routine immunization during the coronavirus disease pandemic in Papua New Guinea during 2020–2022. Methods: In June 2020, 13 provinces of Papua New Guinea were selected to undergo a vaccination catch-up programme, with technical support from the World Health Organization (WHO) and the United Nations Children’s Fund. Twelve provinces received financial and logistic support through the Accelerated Immunization and Health Systems Strengthening programme, and one received support from WHO. All stakeholders were involved in planning and implementing the catch-up programme. Results: Between July 2020 and June 2022, about 340 health facilities conducted catch-up activities. The highest number of children aged under 1 year were vaccinated in 2022 (n = 33 652 for third dose of pentavalent vaccine). The national coverage of routine immunization (including the catch-up vaccinations) increased between 2019 and 2020 – by 5% for the third dose of pentavalent vaccine, 11% for the measles-rubella vaccine and 16% for the inactivated poliovirus vaccine. The coverage declined slightly in 2021 before increasing again in 2022. Discussion: The catch-up programme was an instrumental tool to improve routine immunization coverage between 2020 and 2022 and during the pandemic in Papua New Guinea. With appropriate technical and logistic support, including financial and human resources, catch-up programmes can strengthen routine immunization coverage across the country.
Assuntos
Surtos de Doenças , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Antituberculosos/uso terapêutico , Países em Desenvolvimento , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Avaliação das Necessidades , Papua Nova Guiné/epidemiologia , Prevalência , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Tuberculose Resistente a Múltiplos Medicamentos/diagnósticoRESUMO
Issue:Papua New Guinea is striving to achieve the minimum core requirements under the International Health Regulations in surveillance and outbreak response, and has experienced challenges in the availability and distribution of health professionals.Context:Since mid-2009, a large cholera outbreak spread across lowland regions of the country and has been associated with more than 15 500 notifications at a case fatality ratio of 3.2%. The outbreak placed significant pressure on clinical and public health services.Action:We describe some of the challenges to cholera preparedness and response in this human resource-limited setting, the strategies used to ensure effective cholera management and lessons learnt.Outcome:Cholera task forces were useful to establish a clear system of leadership and accountability for cholera outbreak response and ensure efficiencies in each technical area. Cholera outbreak preparedness and response was strongest when human resource and health systems functioned well before the outbreak. Communication relied on coordination of existing networks and methods for empowering local leaders and villagers to modify behaviours of the population.Discussion:In line with the national health emergencies plan, the successes of human resource strategies during the cholera outbreak should be built upon through emergency exercises, especially in non-affected provinces. Population needs for all public health professionals involved in health emergency preparedness and response should be mapped, and planning should be implemented to increase the numbers in relevant areas. Human resource planning should be integrated with health emergency planning. It is essential to maintain and strengthen the human resource capacities and experiences gained during the cholera outbreak to ensure a more effective response to the next health emergency.