Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: a descriptive epidemiological study.

BACKGROUND: Plasmodium falciparum is an apicomplexan parasite responsible for lethal cases of malaria. According to WHO recommendations, P falciparum cases are treated with artemisinin-based combination therapy including dihydroartemisinin-piperaquine. However, the emergence of resistant parasites against dihydroartemisinin-piperaquine was reported in southeast Asia in 2008 and, a few years later, suspected in South America. METHODS: To characterise resistance emergence, a treatment efficacy study was performed on the reported patients infected with P falciparum and treated with dihydroartemisinin-piperaquine in French Guiana (n=6, 2016-18). Contemporary isolates collected in French Guiana were genotyped for P falciparum chloroquine resistance transporter (pfCRT; n=845) and pfpm2 and pfpm3 copy number (n=231), phenotyped using the in vitro piperaquine survival assay (n=86), and analysed through genomic studies (n=50). Additional samples from five Amazonian countries and one outside the region were genotyped (n=1440). FINDINGS: In field isolates, 40 (47%) of 86 (95% CI 35·9-57·1) were resistant to piperaquine in vitro; these phenotypes were more associated with pfCRTC350R (ie, Cys350Arg) and pfpm2 and pfpm3 amplifications (Dunn test, p<0·001). Those markers were also associated with dihydroartemisinin-piperaquine treatment failure (n=3 [50%] of 6). A high prevalence of piperaquine resistance markers was observed in Suriname in 19 (83%) of 35 isolates and in Guyana in 579 (73%) of 791 isolates. The pfCRTC350R mutation emerged before pfpm2 and pfpm3 amplification in a temporal sequence different from southeast Asia, and in the absence of artemisinin partial resistance, suggesting a geographically distinctive epistatic relationship between these genetic markers. INTERPRETATION: The high prevalence of piperaquine resistance markers in parasite populations of the Guianas, and the risk of associated therapeutic failures calls for caution on dihydroartemisinin-piperaquine use in the region. Furthermore, greater attention should be given to potential differences in genotype to phenotype mapping across genetically distinct parasite populations from different continents. FUNDING: Pan American Health Organization and WHO, French Ministry for Research, European Commission, Santé publique France, Agence Nationale de la Recherche, Fundação de Amparo à Pesquisa do Estado do Amazonas, Ministry of Health of Brazil, Oswaldo Cruz Foundation, and National Institutes of Health. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Evaluating elimination of mother-to-child transmission of HIV in Suriname: a mixed method study.

Objectives: To evaluate the cascade of care for the elimination of mother-to-child-transmission of human immunodeficiency virus (HIV) in Suriname and identify sociodemographic and clinical factors preventing transmission to exposed infants. Methods: A mixed-methods study design was used. Antenatal care data from the 2018 cross-sectional multi-indicator cluster survey on 1 026 women aged 15-49 years who had had a live birth in the previous 2 years were used. Furthermore, national data on a cohort of 279 mothers with HIV and their 317 infants born from 2016 to 2018 were evaluated. Additionally, 13 cases of mother-to-child-transmission of HIV were reviewed. Results: In 89.3% of cases, no mother-to-child HIV transmission occurred. Early cascade steps show that 28.4% of women had unmet family planning needs, 15% had no antenatal visits, 8% delivered outside a health facility, and 71.5% received an HIV test during antenatal care. Of the pregnant women with HIV, 84.2% received antiretroviral therapy, while 95.5% of their infants received HIV prophylactic treatment. Receiving antiretroviral therapy for the mother (odds ratio (OR) 45.4, 95% confidence interval (CI) 9.6-215.3) and the child (OR 145.7, 95% CI 14.4-1477.4) significantly increased the odds of a negative HIV test result in infants. Conversely, living in the interior decreased the odds (OR 0.2, 95% CI 0.4-0.7) compared with urban living. Conclusions: HIV medication for mothers with HIV and their infants remains key in the prevention of mother-to-child-transmission of HIV. Early prenatal care with follow-up should be strengthened in Suriname.

Evaluating elimination of mother-to-child transmission of HIV in Suriname: a mixed method study / Estudio con métodos mixtos para evaluar la eliminación de la transmisión maternoinfantil del VIH en Suriname / Avaliação da eliminação da transmissão materno-infantil do HIV no Suriname: estudo de métodos mistos

[ABSTRACT]. Objectives. To evaluate the cascade of care for the elimination of mother-to-child-transmission of human immunodeficiency virus (HIV) in Suriname and identify sociodemographic and clinical factors preventing transmission to exposed infants. Methods. A mixed-methods study design was used. Antenatal care data from the 2018 cross-sectional multi- indicator cluster survey on 1 026 women aged 15–49 years who had had a live birth in the previous 2 years were used. Furthermore, national data on a cohort of 279 mothers with HIV and their 317 infants born from 2016 to 2018 were evaluated. Additionally, 13 cases of mother-to-child-transmission of HIV were reviewed. Results. In 89.3% of cases, no mother-to-child HIV transmission occurred. Early cascade steps show that 28.4% of women had unmet family planning needs, 15% had no antenatal visits, 8% delivered outside a health facility, and 71.5% received an HIV test during antenatal care. Of the pregnant women with HIV, 84.2% received antiretroviral therapy, while 95.5% of their infants received HIV prophylactic treatment. Receiving antiretroviral therapy for the mother (odds ratio (OR) 45.4, 95% confidence interval (CI) 9.6–215.3) and the child (OR 145.7, 95% CI 14.4–1477.4) significantly increased the odds of a negative HIV test result in infants. Conversely, living in the interior decreased the odds (OR 0.2, 95% CI 0.4–0.7) compared with urban living. Conclusions. HIV medication for mothers with HIV and their infants remains key in the prevention of mother- to-child-transmission of HIV. Early prenatal care with follow-up should be strengthened in Suriname.

[RESUMEN]. Objetivos. Evaluar la secuencia de la atención para la eliminación de la transmisión maternoinfantil del virus de la inmunodeficiencia humana (VIH) en Suriname y determinar los factores sociodemográficos y clínicos que previenen la transmisión a lactantes expuestos al virus. Métodos. En este estudio se empleó un diseño de métodos mixtos. Se utilizaron los datos de atención prena- tal procedentes de la encuesta transversal de indicadores múltiples por conglomerados del 2018, realizada en 1 026 mujeres de entre 15 y 49 años que habían dado a luz a un nacido vivo en los dos años anteriores. También se evaluaron los datos nacionales correspondientes a una cohorte de 279 madres con infección por el VIH y sus 317 bebés nacidos entre el 2016 y el 2018. Además, se analizaron en detalle 13 casos de trans- misión maternoinfantil del VIH. Resultados. En el 89,3% de los casos no hubo transmisión maternoinfantil del VIH. En las etapas iniciales de la secuencia de la atención se observó que el 28,4% de las mujeres no tenían cubiertas sus necesidades de planificación familiar; además, el 15% no dispusieron de consultas de atención prenatal, el 8% dieron a luz fuera de un centro de salud y en el 71,5% se llevó a cabo una prueba de detección del VIH en el marco de la atención prenatal. De las mujeres embarazadas con infección por el VIH, el 84,2% recibió un tratamiento antirretroviral, mientras que el 95,5% de los bebés recibieron un tratamiento profiláctico contra el VIH. La administración de tratamiento antirretroviral a la madre (cociente de posibilidades [OR] = 45,4; intervalo de confianza [IC] del 95%: 9,6-215,3) y al bebé (OR = 145,7; IC del 95%: 14,4-1477,4) hizo que aumentaran significativamente las posibilidades de obtener un resultado negativo en la prueba de detección del VIH en los lactantes. Por el contrario, residir en el interior del país hizo que disminuyeran dichas posibilidades (OR = 0,2; IC del 95%: 0,4-0,7), en comparación con residir en un entorno urbano. Conclusiones. Para las madres con infección por el VIH y para sus bebés, los medicamentos contra el VIH siguen siendo esenciales para prevenir la transmisión maternoinfantil del VIH. En Suriname debe reforzarse la atención prenatal temprana, incluido el seguimiento.

[RESUMO]. Objetivos. Avaliar a cascata de atendimento para a eliminação da transmissão materno-infantil do vírus da imunodeficiência humana (HIV) no Suriname e identificar fatores sociodemográficos e clínicos que impedem a transmissão a bebês expostos. Métodos. Foi utilizado um delineamento de estudo com métodos mistos. Foram usados dados de atendi- mento pré-natal de uma pesquisa de indicadores múltiplos por conglomerados de corte transversal realizada em 2018, que incluiu 1 026 mulheres com idades entre 15 e 49 anos que haviam tido um nascido vivo nos dois anos anteriores. Além disso, foram avaliados os dados nacionais de uma coorte de 279 mães com HIV e seus 317 bebês nascidos vivos de 2016 a 2018, além de 13 casos de transmissão materno-infantil de HIV. Resultados. Em 89,3% dos casos, não houve transmissão materno-infantil do HIV. As etapas iniciais da cas- cata demonstram que 28,4% das mulheres tiveram necessidades não atendidas de planejamento familiar, 15% não fizeram consultas pré-natais, 8% tiveram o parto fora de uma unidade de saúde e 71,5% receberam um teste de HIV durante o atendimento pré-natal. Das gestantes com HIV, 84,2% receberam terapia antirre- troviral, e 95,5% de seus bebês receberam tratamento profilático para o HIV. O tratamento antirretroviral da mãe (razão de chances [RC]: 45,4; intervalo de confiança [IC] de 95%: 9,6–215,3) e da criança (RC: 145,7; IC 95%: 14,4–1477,4) aumentou significativamente a probabilidade de um resultado negativo no teste de HIV dos bebês. Por outro lado, morar no interior diminuiu a probabilidade (RC: 0,2; IC 95%: 0,4–0,7) em compa- ração com o ambiente urbano. Conclusões. A medicação de mães e bebês contra o HIV continua sendo fundamental para a prevenção da transmissão materno-infantil do HIV. Deve-se reforçar o atendimento pré-natal precoce com acompanha- mento no Suriname.

Advocating for PCR-RFLP as molecular tool within malaria programs in low endemic areas and low resource settings.

The road to malaria elimination for low- and middle-income countries is paved with obstacles, including the complexity and high costs of advanced molecular methods for genomic analysis. The usefulness of PCR-RFLP as less complex and affordable molecular surveillance tool in low-endemic malaria regions was assessed in a cross-sectional study conducted in Suriname, currently striving for malaria elimination, but plagued by recent P. vivax outbreaks. Molecular analysis of two highly polymorphic genes Pvmsp-1 F2 and Pvmsp-3α was performed for 49 samples, collected during October 2019 through September 2021 from four different regions with varying malaria transmission risks. RFLP-profiling revealed that outbreak samples from three indigenous villages, almost exclusively, harbored a single clonal type, matching the "Palumeu" lineage previously described in 2019, despite multiple relapses and drug pressure exerted by mass drug administration events, suggesting a limited P. vivax hypnozoite reservoir in Suriname. In contrast, isolates originating from Sophie, a mining area in neighboring French Guiana displayed a highly heterogeneous parasite population consistent with its endemic malaria status, demonstrating the differentiating capacity and thus the usefulness of PCR-RFLP for P. vivax genetic diversity studies. Outbreak reconstruction emphasized the impact of undetected human movement and relapses on reintroduction and resurgence of P. vivax malaria and PCR-RFLP monitoring of circulating parasites guided the roll-out of targeted interventions. PCR-RFLP seems a suitable molecular alternative in low-endemic areas with restricted resources for outbreak analysis, for monitoring the spread or containment of circulating strains and for identification of imported cases or potential foci.

Evaluating elimination of mother-to-child transmission of HIV in Suriname: a mixed method study / Estudio con métodos mixtos para evaluar la eliminación de la transmisión maternoinfantil del VIH en Suriname / Avaliação da eliminação da transmissão materno-infantil do HIV no Suriname: estudo de métodos mistos

ABSTRACT Objectives. To evaluate the cascade of care for the elimination of mother-to-child-transmission of human immunodeficiency virus (HIV) in Suriname and identify sociodemographic and clinical factors preventing transmission to exposed infants. Methods. A mixed-methods study design was used. Antenatal care data from the 2018 cross-sectional multi-indicator cluster survey on 1 026 women aged 15-49 years who had had a live birth in the previous 2 years were used. Furthermore, national data on a cohort of 279 mothers with HIV and their 317 infants born from 2016 to 2018 were evaluated. Additionally, 13 cases of mother-to-child-transmission of HIV were reviewed. Results. In 89.3% of cases, no mother-to-child HIV transmission occurred. Early cascade steps show that 28.4% of women had unmet family planning needs, 15% had no antenatal visits, 8% delivered outside a health facility, and 71.5% received an HIV test during antenatal care. Of the pregnant women with HIV, 84.2% received antiretroviral therapy, while 95.5% of their infants received HIV prophylactic treatment. Receiving antiretroviral therapy for the mother (odds ratio (OR) 45.4, 95% confidence interval (CI) 9.6-215.3) and the child (OR 145.7, 95% CI 14.4-1477.4) significantly increased the odds of a negative HIV test result in infants. Conversely, living in the interior decreased the odds (OR 0.2, 95% CI 0.4-0.7) compared with urban living. Conclusions. HIV medication for mothers with HIV and their infants remains key in the prevention of mother-to-child-transmission of HIV. Early prenatal care with follow-up should be strengthened in Suriname.

RESUMEN Objetivos. Evaluar la secuencia de la atención para la eliminación de la transmisión maternoinfantil del virus de la inmunodeficiencia humana (VIH) en Suriname y determinar los factores sociodemográficos y clínicos que previenen la transmisión a lactantes expuestos al virus. Métodos. En este estudio se empleó un diseño de métodos mixtos. Se utilizaron los datos de atención prenatal procedentes de la encuesta transversal de indicadores múltiples por conglomerados del 2018, realizada en 1 026 mujeres de entre 15 y 49 años que habían dado a luz a un nacido vivo en los dos años anteriores. También se evaluaron los datos nacionales correspondientes a una cohorte de 279 madres con infección por el VIH y sus 317 bebés nacidos entre el 2016 y el 2018. Además, se analizaron en detalle 13 casos de transmisión maternoinfantil del VIH. Resultados. En el 89,3% de los casos no hubo transmisión maternoinfantil del VIH. En las etapas iniciales de la secuencia de la atención se observó que el 28,4% de las mujeres no tenían cubiertas sus necesidades de planificación familiar; además, el 15% no dispusieron de consultas de atención prenatal, el 8% dieron a luz fuera de un centro de salud y en el 71,5% se llevó a cabo una prueba de detección del VIH en el marco de la atención prenatal. De las mujeres embarazadas con infección por el VIH, el 84,2% recibió un tratamiento antirretroviral, mientras que el 95,5% de los bebés recibieron un tratamiento profiláctico contra el VIH. La administración de tratamiento antirretroviral a la madre (cociente de posibilidades [OR] = 45,4; intervalo de confianza [IC] del 95%: 9,6-215,3) y al bebé (OR = 145,7; IC del 95%: 14,4-1477,4) hizo que aumentaran significativamente las posibilidades de obtener un resultado negativo en la prueba de detección del VIH en los lactantes. Por el contrario, residir en el interior del país hizo que disminuyeran dichas posibilidades (OR = 0,2; IC del 95%: 0,4-0,7), en comparación con residir en un entorno urbano. Conclusiones. Para las madres con infección por el VIH y para sus bebés, los medicamentos contra el VIH siguen siendo esenciales para prevenir la transmisión maternoinfantil del VIH. En Suriname debe reforzarse la atención prenatal temprana, incluido el seguimiento.

RESUMO Objetivos. Avaliar a cascata de atendimento para a eliminação da transmissão materno-infantil do vírus da imunodeficiência humana (HIV) no Suriname e identificar fatores sociodemográficos e clínicos que impedem a transmissão a bebês expostos. Métodos. Foi utilizado um delineamento de estudo com métodos mistos. Foram usados dados de atendimento pré-natal de uma pesquisa de indicadores múltiplos por conglomerados de corte transversal realizada em 2018, que incluiu 1 026 mulheres com idades entre 15 e 49 anos que haviam tido um nascido vivo nos dois anos anteriores. Além disso, foram avaliados os dados nacionais de uma coorte de 279 mães com HIV e seus 317 bebês nascidos vivos de 2016 a 2018, além de 13 casos de transmissão materno-infantil de HIV. Resultados. Em 89,3% dos casos, não houve transmissão materno-infantil do HIV. As etapas iniciais da cascata demonstram que 28,4% das mulheres tiveram necessidades não atendidas de planejamento familiar, 15% não fizeram consultas pré-natais, 8% tiveram o parto fora de uma unidade de saúde e 71,5% receberam um teste de HIV durante o atendimento pré-natal. Das gestantes com HIV, 84,2% receberam terapia antirretroviral, e 95,5% de seus bebês receberam tratamento profilático para o HIV. O tratamento antirretroviral da mãe (razão de chances [RC]: 45,4; intervalo de confiança [IC] de 95%: 9,6-215,3) e da criança (RC: 145,7; IC 95%: 14,4-1477,4) aumentou significativamente a probabilidade de um resultado negativo no teste de HIV dos bebês. Por outro lado, morar no interior diminuiu a probabilidade (RC: 0,2; IC 95%: 0,4-0,7) em comparação com o ambiente urbano. Conclusões. A medicação de mães e bebês contra o HIV continua sendo fundamental para a prevenção da transmissão materno-infantil do HIV. Deve-se reforçar o atendimento pré-natal precoce com acompanhamento no Suriname.

Reconstruction of Plasmodium vivax outbreaks in a low malaria endemic setting utilizing conventional restriction fragment length polymorphism.

Suriname is on track to eliminate local malaria transmission. P. vivax malaria reemerged in March and September 2019 in the Amerindian village Palumeu, free of malaria for two years and concurrently, a case was reported in another village Alalaparoe. The outbreaks were contained through targeted interventions including Mass Drug Administration (MDA). Molecular outbreak analysis was performed on 23 dried blood spots (DBS) using combined polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) with Pvmsp-1 F2 and Pvmsp-3α as polymorphic marker genes. Independent controls substantiated the discriminating capacities of the utilized PCR-RFLP method. All isolates from the first and second Palumeu outbreak shared a distinctive haplotype presuming single clonal lineage. An imported case probably triggered the first outbreak, while a delayed episode, prompted by withdrawal of drug pressure at the end of the prophylactic MDA, was suggested as source of the second outbreak. A diverging variant was demonstrated in Alalaparoe, implicating an infection from a different source. PCR-RFLP proved to be a useful molecular tool for P. vivax outbreak management in low endemic malaria settings.

Epidemiology of respiratory viruses in patients with severe acute respiratory infections and influenza-like illness in Suriname.

BACKGROUND: Influenza has been well studied in developed countries with temperate climates, in contrast to low- and middle-income (LMIC) countries, thus hampering the effort to attain representative global data. Furthermore, data on non-influenza respiratory infections are also limited. Insight in viral respiratory infections in Suriname, a tropical LMIC in South America, would contribute to improved local preventive measures and a better global understanding of respiratory viruses. METHODS: From May 2016 through April 2018, all patients (n = 1096) enrolled in the national severe acute respiratory infection and influenza-like illness surveillance were screened for the presence of 10 respiratory viruses with singleplex RT-PCR. RESULTS: The overall viral-positive detection rate was 45.3%, specified as RSV (19.4%), influenza (15.5%), hMPV (4.9%), AdV (4.6%), and parainfluenza (3.8%). Co-infections were detected in 6.2% of the positive cases. Lower overall positivity was observed in the SARI vs ILI surveillance and influenza prevalence was higher in outpatients (45.0% vs 6.7%), while RSV exhibited the reverse (4.8% vs 23.8%). Respiratory infections in general were more common in children than in adults (54.4% vs 29.5%), although children were significantly less affected by influenza (11.5% vs 22.7%). None of the respiratory viruses displayed a clear seasonal pattern, and viral interference was observed between RSV and influenza. CONCLUSIONS: The comprehensive information presented for Suriname, including first data on non-influenza respiratory viruses, displayed distinct differences between the viruses, in seasonality, within age groups and between SARI/ILI, accentuating the need, especially for tropical LMIC countries to continue ongoing surveillance and accumulate local data.

First Assessment of Acquired HIV-1 Drug Resistance and Mutation Patterns in Suriname.

HIV drug resistance testing is fundamental in clinical patient management, but data on HIV-1 drug-resistant mutations (DRMs) is scarce in the Caribbean and in Suriname limited to one survey on transmitted resistance. The aim of this study was to address this gap, to gain insight in acquired HIV drug resistance (ADR) prevalence and mutation patterns, and to improve HIV-1 treatment outcome of people living with HIV (PLHIV) in Suriname. A prospective cross-sectional study was conducted from July 2018 through January 2019 among treatment-experienced PLHIV (n = 72), with either treatment failure or antiretroviral therapy restart. Genotypic drug resistance testing was performed and DRM impact on drug effectiveness was examined. Genotypic drug resistance testing revealed 97.2% HIV-1 subtype B, 2.8% B/D recombinants and a ADR prevalence of 63.2% in treatment failure patients, with a predominance of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. The most common DRMs were M184V (23.6%) and K103N (18.8%). A high level of non-DRM polymorphisms was observed in both the reverse transcriptase (RT) and protease (PR) gene. Interesting deviations from the existing mutation datasets were noted at position E248 and R83 of the RT gene and L63 and V77 in the PR gene. Full susceptibility to all examined drugs was 54.2%, while high-level drug resistance was estimated at 37.5%, which seems promising for treatment outcomes for PLHIV in Suriname, although cross-resistance to next-generation NNRTIs was already estimated for nearly a quarter of the patients. The meager 2.9% of PR DRMs rendered protease inhibitors as an effective rescue HIV-1 treatment.

Malaria serology data from the Guiana shield: first insight in IgG antibody responses to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae antigens in Suriname.

BACKGROUND: Suriname has accomplished a steep decline in malaria burden, even reaching elimination levels. Plasmodium serology data are not available for Suriname and even extremely scarce within the region, therefore malaria serology testing was introduced, country customized cut-off values were determined and a study was performed to explore the antibody status for Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae. METHODS: A cross-sectional survey was conducted between July 2017 and March 2018 in two areas of the interior with different malaria settings: Stoelmanseiland, representing Maroon villages and Benzdorp, a gold mining area, with mostly Brazilian miners. Dried blood spots (DBS) were collected (n = 197) and antibody presence against seven Plasmodium antigens was detected using a multiplex bead-based, IgG antibody assay. Demographic information was gathered through a questionnaire. Country customized cut-off values were generated from a Surinamese malaria-naïve reference population (n = 50). RESULTS: Serological analysis for the reference population revealed cut-off values ranging from 14 MFI for LSA-1 to 177 MFI for PmMSP-119. Seroprevalence against any of the three MSP-119 antibodies was similar in both regions and surpassed 75%. Single seropositivity against PfMSP-119 antibodies was higher in Stoelmanseiland (27.0%) than Benzdorp (9.3%), in line with the historical malaria burden of Stoelmanseiland, while the reverse was observed for PvMSP-119 antibodies. Despite sporadic reports of P. malariae infections, PmMSP-119 antibody presence was 39.6%. A more detailed examination of P. falciparum serology data displayed a higher seroprevalence in villagers (90.7%) than in Brazilians (64.6%) and a highly diverse antigenic response with 22 distinct antibody combinations. CONCLUSIONS: The results on the malaria antibody signature of Maroon villagers and Brazilian miners living in Suriname displayed a high Plasmodium seroprevalence, especially for P. falciparum in villagers, still reflecting the historical malaria burden. The seroprevalence data for both regions and the observed combinations of P. falciparum antibodies provided a valuable dataset from a historically important region to the international malaria serology knowledge. First insight in malaria serology data for Suriname indicated that the use of other target groups and assessment of age-dependent seroprevalence are required to successfully use malaria serology as tool in the national elimination strategy.

Archival, paleopathological and aDNA-based techniques in leprosy research and the case of Father Petrus Donders at the Leprosarium 'Batavia', Suriname.

OBJECTIVE: We assessed whether Petrus Donders (died 1887), a Dutch priest who for 27 years cared for people with leprosy in the leprosarium Batavia, Suriname, had evidence of Mycobacterium (M.) leprae infection. A positive finding of M. leprae ancient (a)DNA would contribute to the origin of leprosy in Suriname. MATERIALS: Skeletal remains of Father Petrus Donders; two additional skeletons excavated from the Batavia cemetery were used as controls. METHODS: Archival research, paleopathological evaluation and aDNA-based testing of skeletal remains. RESULTS: Neither archives nor inspection of Donders skeletal remains revealed evidence of leprosy, and aDNA-based testing for M. leprae was negative. We detected M. leprae aDNA by RLEP PCR in one control skeleton, which also displayed pathological lesions compatible with leprosy. The M. leprae aDNA was genotyped by Sanger sequencing as SNP type 4; the skeleton displayed mitochondrial haplogroup L3. CONCLUSION: We found no evidence that Donders contracted leprosy despite years of intense leprosy contact, but we successfully isolated an archaeological M. leprae aDNA sample from a control skeleton from South America. SIGNIFICANCE: We successfully genotyped recovered aDNA to a M. leprae strain that likely originated in West Africa. The detected human mitochondrial haplogroup L3 is also associated with this geographical region. This suggests that slave trade contributed to leprosy in Suriname. LIMITATIONS: A limited number of skeletons was examined. SUGGESTIONS FOR FURTHER RESEARCH: Broader review of skeletal collections is advised to expand on diversity of the M. leprae aDNA database.

Primaquine double dose for 7 days is inferior to single-dose treatment for 14 days in preventing Plasmodium vivax recurrent episodes in Suriname.

BACKGROUND: Recurrent episodes of Plasmodium vivax are caused by dormant liver stages of the parasite, which are not eradicated by choloroquine. Therefore, effective treatment also includes the use of primaquine (PQ). However, this secondary preventive therapy is often not effective, mostly due to poor adherence to the relatively long treatment course, justifying a comparative study of the efficacy of different durations of PQ treatment. MATERIALS AND METHODS: We included patients presenting with an acute and documented P. vivax infection from January 2006 to February 2008. All patients received chloroquine 25 mg/kg over a 3-day period. Subsequently, patients in group 7D received PQ 30 mg/day for 7 days, and patients in group 14D received standard PQ 15 mg/day for 14 days. All doses were given under supervision and patients were followed up for at least 6 months. The Kaplan-Meier method was used to estimate cumulative probability of recurrence up to 12 months after treatment initiation stratified by treatment group. Cox regression was used to assess possible determinants for recurrent parasitemia. RESULTS: Forty-seven of the 79 included patients (59.5%) were allocated to group 7D and 32 patients (40.5%) were allocated to group 14D. Recurrent parasitemia was detected in 31.9% of the cases in group 7D compared to 12.5% of the cases in group 14D (hazard ratio [HR] =3.36, 95% CI 1.11-10.16). Cumulative probability for recurrent parasitemia at 3, 6, and 12 months was 0.201 (95% CI 0.106-0.362), 0.312 (95% CI 0.190-0.485), and 0.424 (95% CI 0.274-0.615) for group 7D and 0.100 (95% CI 0.033-0.279), 0.100 (95% CI 0.033-0.279), and 0.138 (95% CI 0.054-0.327) for group 14D, respectively. When adjusted for possible confounders, differences in recurrent parasitemia remained significant between the two regimens in Cox regression analysis. CONCLUSION: More than 30% of the patients receiving shorter treatment course had recurrent parasitemia, suggesting that the standard dose of 15 mg/day PQ for 14 days is more efficacious than 30 mg for 7 days in preventing P. vivax recurrent episodes. Furthermore, we suggest that P. vivax treatment in Suriname should be changed to PQ 30 mg/day for 14 days, as per Center for Disease Control and Prevention recommendation, in light of a recurrence rate of over 10%, even in group 14D.

Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname.

In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum We genotyped the PfK13 propeller domain of P. falciparum in 40 samples as well as other mutations proposed to be associated with artemisinin-resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia, but we found fixed resistance mutations for chloroquine (CQ) and sulfadoxine-pyrimethamine. Additionally, the PfCRT C350R mutation, associated with reversal of CQ resistance and piperaquine-selective pressure, was present in 62% of the samples. Our results from neutral microsatellite data also confirmed a high parasite gene flow in the Guiana Shield. Although recruiting participants for therapeutic efficacy studies is challenging in areas where malaria endemicity is very low due to the low number of malaria cases reported, conducting these studies along with molecular surveillance remains essential for the monitoring of artemisinin-resistant alleles and for the characterization of the population structure of P. falciparum in areas targeted for malaria elimination.

Assessing parasite clearance during uncomplicated Plasmodium falciparum infection treated with artesunate monotherapy in Suriname.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life. METHODS: The study was conducted in Paramaribo, the capital of Suriname, from July 2013 until July 2014. Patients with uncomplicated Plasmodium falciparum infection were included and received artesunate mono-therapy for three days. Day 3 parasitaemia, treatment outcome after 28 days and parasite half-life were determined. The latter was assessed with the parasite clearance estimator from the WorldWide Antimalarial Resistance Network (WWARN). RESULTS: Thirty-nine patients were included from July 2013 until July 2014. The day 3 parasitemia was 10%. Eight patients (20.5%) could be followed up until day 28 and showed adequate clinical and parasitological response. Parasite half-life could only be determined from ten data series (25.7%). The median parasite half-life was 5.16 hours, and seven of these data series had a half-life ≥5 hours, still comprising 17.9% of the total data series. CONCLUSION: The low follow-up rate and the limited analyzable data series preclude clear conclusions about the efficacy of artesunate monotherapy in Suriname and the parasite half-life, respectively. The emergence of at least 17.9% of data series with a parasite half-life ≥5 hours supports the possible presence of artemisinin resistance.

HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname.

The molecular epidemiologic profile of HIV-1 in Suriname was determined through protease (PR) and reverse transcriptase (RT) sequences obtained from HIV-1 strains collected from 100 drug-naive HIV-1-infected persons. Subtype determination revealed that most viruses were of subtype B (94.9%) in both PR and RT genomic regions, followed by B/D recombinants (5.1%). Analysis of drug resistance mutations showed only one transmitted dug resistance mutation (TDRM) (V75M) in a single strain. The genetic data obtained can serve as a baseline for Suriname to monitor emerging mutations. This study reveals that the HIV-1 epidemic in Suriname is still characterized by a low TDRM rate (1%) and a low level of subtype diversity. However, both genes display a high genetic polymorphism. This high polymorphism may ultimately lead to drug resistance. Continuous monitoring of the baseline resistance is therefore a prerequisite to safeguard effective long-term treatment for people living with HIV-1 in Suriname.

First Chikungunya Outbreak in Suriname; Clinical and Epidemiological Features.

BACKGROUND: In June 2014, Suriname faced the first Chikungunya outbreak. Since international reports mostly focus on hospitalized patients, the least affected group, a study was conducted to describe clinical characteristics of mainly outpatients including children. In addition, the cumulative incidence of this first epidemic was investigated. METHODOLOGY: During August and September 2014, clinically suspected Chikungunya cases were included in a prospective follow-up study. Blood specimens were collected and tested for viral RNA presence. Detailed clinical information was gathered through multiple telephone surveys until day 180. In addition, a three stage household-based cluster with a cross-sectional design was conducted in October, December 2014 and March 2015 to assess the cumulative incidence. PRINCIPAL FINDINGS: Sixty-eight percent of symptomatic patients tested positive for Chikungunya virus (CHIKV). Arthralgia and pain in the fingers were distinctive for viremic CHIKV infected patients. Viremic CHIKV infected children (≤12 years) characteristically displayed headache and vomiting, while arthralgia was less common at onset. The disease was cleared within seven days by 20% of the patients, while 22% of the viremic CHIKV infected patients, mostly women and elderly reported persistent arthralgia at day 180. The extrapolated cumulative CHIKV incidence in Paramaribo was 249 cases per 1000 persons, based on CHIKV self-reported cases in 53.1% of the households and 90.4% IgG detected in a subset of self-reported CHIKV+ persons. CHIKV peaked in the dry season and a drastic decrease in CHIKV patients coincided with a governmental campaign to reduce mosquito breeding sites. CONCLUSIONS/SIGNIFICANCE: This study revealed that persistent arthralgia was a concern, but occurred less frequently in an outpatient setting. The data support a less severe pathological outcome for Caribbean CHIKV infections. This study augments incidence data available for first outbreaks in the region and showed that actions undertaken at the national level to mount responses may have positively impacted containment of this CHIKV outbreak.

First Chikungunya outbreak in Suriname: Clinical and epidemiological features

Background In June 2014, Suriname faced the first Chikungunya outbreak. Since international reports mostly focus on hospitalized patients, the least affected group, a study was conducted to describe clinical characteristics of mainly outpatients including children. In addition, the cumulative incidence of this first epidemic was investigated. Methodology During August and September 2014, clinically suspected Chikungunya cases were included in a prospective follow-up study. Blood specimens were collected and tested for viral RNA presence. Detailed clinical information was gathered through multiple telephone surveys until day 180. In addition, a three stage household-based cluster with a cross-sectional design was conducted in October, December 2014 and March 2015 to assess the cumulative incidence. Principal Findings Sixty-eight percent of symptomatic patients tested positive for Chikungunya virus (CHIKV). Arthralgia and pain in the fingers were distinctive for viremic CHIKV infected patients. Viremic CHIKV infected children (≤12years) characteristically displayed headache and vomiting, while arthralgia was less common at onset. The disease was cleared within seven days by 20% of the patients, while 22% of the viremic CHIKV infected patients, mostly women and elderly reported persistent arthralgia at day 180. The extrapolated cumulative CHIKV incidence in Paramaribo was 249 cases per 1000 persons, based on CHIKV self-reported cases in 53.1% of the households and 90.4% IgG detected in a subset of self-reported CHIKV+ persons. CHIKV peaked in the dry season and a drastic decrease in CHIKV patients coincided with a governmental campaign to reduce mosquito breeding sites. Conclusions/Significance This study revealed that persistent arthralgia was a concern, but occurred less frequently in an outpatient setting. The data support a less severe pathological outcome for Caribbean CHIKV infections. This study augments incidence data available for first outbreaks in the region and showed that actions undertaken at the national level to mount responses may have positively impacted containment of this CHIKV outbreak.

Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname.

Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or unavailable. Recent reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests specific for detection of P. falciparum may provide false negative results in some parts of South America due to the emergence of P. falciparum parasites that lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes were amplified in parasite isolates collected from Guyana and Suriname to determine if there were circulating isolates with deletions in these genes. Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97 isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3-positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the flanking genes. We also investigated the population substructure of the isolates collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3 belonged to any genetic subtypes. Cluster analysis revealed that there was no predominant P. falciparum population substructure among the isolates from either country, an indication of genetic admixture among the parasite populations. Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a single, unique genetic background.

Gold mining areas in Suriname: reservoirs of malaria resistance?

BACKGROUND: At present, malaria cases in Suriname occur predominantly in migrants and people living and/or working in areas with gold mining operations. A molecular survey was performed in Plasmodium falciparum isolates originating from persons from gold mining areas to assess the extent and role of mining areas as reservoirs of malaria resistance in Suriname. METHODS: The status of 14 putative resistance-associated single nucleotide polymorphisms in the pfdhfr, pfcrt, pfmdr1, and pfATP6 genes was assessed for 28 samples from gold miners diagnosed with P. falciparum malaria using polymerase chain reaction amplification and restriction fragment length polymorphism analysis, and the results were compared with earlier data from nonmining villagers. RESULTS: Isolates from miners showed a high degree of homogeneity, with a fixed pfdhfr Ile51/Asn108, pfmdr1 Phe184/Asp1042/Tyr1246, and pfcrt Thr76 mutant genotype, while an exclusively wild-type genotype was observed for pfmdr1 Asn86 and pfdhfr Ala16, Cys59, and Ile164, and for the pfATP6 positions Leu263/Ala623/Ser769. Small variations were observed for pfmdr1 S1034C. No statistically significant difference could be detected in allele frequencies between mining and nonmining villagers. CONCLUSION: Despite the increased risk of malaria infection in individuals working/living in gold mining areas, we did not detect an increase in mutation frequency at the 14 analyzed single nucleotide polymorphisms. Therefore, mining areas in Suriname cannot yet be considered as reservoirs for malaria resistance.

Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.

Molecular surveillance as monitoring tool for drug-resistant Plasmodium falciparum in Suriname.

The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.