Epidemiology of malaria in a village in the Rufiji River Delta, Tanzania: declining transmission over 25 years revealed by different parasitological metrics

Background: Assessments of the epidemiology of malaria over time are needed to understand changes in transmission and guide control and elimination strategies. Methods: A longitudinal population study was established in 1985 in Nyamisati village in the Rufiji River Delta, Tanzania. A physician and research team lived in the village 1984–2000. Parasite prevalence by microscopy and two PCR methods, spleen rates and haemoglobin levels were measured in repeated cross-sectional surveys between 1985 and 2010. Passive surveillance of malaria cases was maintained until end 1999. Bed nets were distributed after the surveys 1993, 1999 and 2010. Results: In 1985, overall parasite prevalence by microscopy was 70% (90% in children ages two to nine years). The prevalence decreased gradually by microscopy (38.9% 1994, 26.7% 1999) and msp2-PCR (58.7% 1994, 44.8% 1999), whereas real-time PCR prevalence remained higher throughout the 1990s (69.4% 1994, 64.8% 1999). In 2010, parasite prevalence was 17.8% by real-time PCR and 16.3% by msp2-PCR, and estimated to 4.8% by microscopy. Spleen rates in children ages two to nine years decreased earlier than parasite prevalence, from \u3e75 to 42% in the 1980s, to nil during the 1990s. The prevalence of severe and moderate anaemia decreased from 41.1 to 13.1%. No deaths at the time of acute malaria were recorded when the research team lived in the village. Conclusions:A marked decline in malaria transmission was observed over 25 years. The decrease was detected after the arrival of the research team and continued gradually both before and after distribution of bed nets. Spleen rates and microscopy identified early changes when transmission was still intense, whereas real-time PCR was a more sensitive metric when transmission was reduced. The study provides historical data on malaria within a closely monitored rural village and contributes to the understanding of changing epidemiology in sub-Saharan Africa

Persistent transmission of Plasmodium malariae and Plasmodium ovale species in an area of declining Plasmodium falciparum transmission in eastern Tanzania

A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium species, current focus is mainly directed towards Plasmodium falciparum, and to a lesser extent P. vivax. There is a substantial lack of data on both global and local transmission patterns of the neglected malaria parasites P. malariae and P. ovale spp. We used a species-specific real-time PCR assay targeting the Plasmodium 18s rRNA gene to evaluate temporal trends in the prevalence of all human malaria parasites over a 22-year period in a rural village in Tanzania.We tested 2897 blood samples collected in five cross-sectional surveys conducted between 1994 and 2016. Infections with P. falciparum, P. malariae, and P. ovale spp. were detected throughout the study period, while P. vivax was not detected. Between 1994 and 2010, we found a more than 90% reduction in the odds of infection with all detected species. The odds of P. falciparum infection was further reduced in 2016, while the odds of P. malariae and P. ovale spp. infection increased 2- and 6-fold, respectively, compared to 2010. In 2016, non-falciparum species occurred more often as mono-infections. The results demonstrate the persistent transmission of P. ovale spp., and to a lesser extent P. malariae despite a continued decline in P. falciparum transmission. This illustrates that the transmission patterns of the non-falciparum species do not necessarily follow those of P. falciparum, stressing the need for attention towards non-falciparum malaria in Africa. Malaria elimination will require a better understanding of the epidemiology of P. malariae and P. ovale spp. and improved tools for monitoring the transmission of all Plasmodium species, with a particular focus towards identifying asymptomatic carriers of infection and designing appropriate interventions to enhance malaria control. Author summary The reduction in the global burden of malaria has encouraged efforts for elimination. Attempts to control and monitor transmission have mainly focused on the predominant malaria parasites Plasmodium falciparum and P. vivax. However, eliminating malaria requires the elimination of all human malaria parasites and limited interest has been directed towards estimating the disease burden attributable to the neglected malaria parasites P. ovale spp. and P. malariae. The authors used molecular methods to analyse 2897 blood samples collected in five cross-sectional surveys over a period of 22 years, and described the transmission patterns of all human malaria parasites in a Tanzanian village. They demonstrate a persistent transmission of P. malariae and P. ovale spp. despite a substantial reduction in transmission of P. falciparum, highlighting the need for more attention towards non-falciparum malaria. The authors discuss the implications of these findings in the context of current efforts for regional malaria elimination

Impact of pre-diagnosis awareness of HIV-related stigma and dispositional coping on linkage to HIV care among newly diagnosed HIV+ Peruvian patients.

A substantial body of literature has characterized how psychosocial factors, including HIV-related stigma and coping, are associated with HIV testing and HIV care utilization post-diagnosis. Less is known about if certain psychosocial characteristics pre-diagnosis may also predict linkage to care among individuals who receive an HIV-positive diagnosis. We examined if pre-diagnosis awareness/perception about HIV-related stigma and dispositional coping styles predicted linkage to HIV care within three months post-diagnosis with a secondary analysis of 604 patients from a randomized controlled trial (Sabes Study). Awareness/perception about HIV-related stigma, dispositional maladaptive and adaptive coping were measured before patients underwent an HIV test. Linkage to care was measured as receipt of care within three months of receiving the diagnosis. After adjusting for covariates, individuals who reported greater dispositional maladaptive coping pre-diagnosis had lower odds of linking to care, OR = 0.82, 95%CI [0.67, 1.00], p = .05. There was also a non-significant inverse association between dispositional adaptive coping pre-diagnosis and linkage to care. These preliminary data suggest the need for further longitudinal research and highlight the potential utility of pre-diagnosis psychosocial assessment and tailored counseling when providing positive HIV diagnosis results

External Validation of a Prognostic Model of Survival for Resected Typical Bronchial Carcinoids

Background This study aimed to assess the reliability and the validity of a prognostic model of survival recently developed by the European Society of Thoracic Surgery Neuroendocrine Tumor Working Group to predict 5-year overall survival after surgical resection of pulmonary typical carcinoid. Methods We retrospectively collected data on 240 consecutive patients (164 men, 76 women; median age, 58 years [interquartile range, 47 to 68]) who underwent curative lung resection for pulmonary typical carcinoid in seven centers between 2000 and 2015. For each patient, we calculated the corresponding risk class (A, B, C, D) using the following variables: male, age, previous malignancy, Eastern Cooperative Oncology Group performance status, peripheral tumor, TNM stage. Kaplan-Meier method, and Cox proportional hazards model were used for the statistical analysis. Results During a median follow-up of 42 months (interquartile range, 11 to 84), the 5-year overall survival was 94.2% (95% confidence interval [CI]: 90.2% to 98.2%); 15 of 240 patients died. A significantly decreasing rate of survival was observed from class A to class D (p = 0.004) with rates of 100% (95% CI: 100% to 100%), 96.3% (95% CI: 88.6% to 98.8%), 86.7% (95% CI: 63.0% to 95.7%), and 33.3% (95% CI: 0.9% to 77.4%), respectively, for class A, B, C, and D. This difference persisted also using clinical stage as a variable in the risk class calculation (p = 0.006). No differences were observed in term of overall survival among TNM stage I, II, and III patients (p = 0.94). Conclusions This prognostic model of survival is easily applicable, it is validated by our independent cohort, and it appears to stratify better than the traditional TNM staging. Therefore, it may be useful in counseling patients about their outcomes from surgical treatment and in tailoring treatment for high-risk patients

Is there a role for traditional nuclear medicine imaging in the management of pulmonary carcinoid tumours?

OBJECTIVES: The clinical utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) and somatostatin receptor scintigraphy (SRS) in pulmonary carcinoids staging is unclear. This study aims to determine the role of FDG-PET and SRS in detecting hilar-mediastinal lymph node metastasis from these tumours. METHODS: We retrospectively collected the data of 380 patients who underwent lung resection for primary pulmonary carcinoid in seven centres between 2000 and 2015. Patients without nodal sampling (n = 78) were excluded. In 302 patients [35% men, median age 58 (interquartile range 47-68) years] the results of preoperative computed tomography (CT) scan, FDG-PET and SRS were analysed and compared to the pathological findings after resection to determine the respective utility of these two nuclear tests. RESULTS: The sensitivity, specificity and negative predictive value in detecting N1 and N2 disease were respectively 33% and 46%, 93% and 90%, 88% and 95% for computed-tomography-scan, 38% and 60%, 93% and 95%, 88% and 95% for FDG-PET, 22% and 33%, 95% and 98%, 84% and 87% for SRS. The diagnostic accuracy for N1 and N2 disease of CT scan was not significantly different from that of FDG-PET (P = 1.0 and P = 0.37 for N1 and N2 disease respectively) and of SRS (P = 0.47 and P = 0.35 for N1 and N2 disease respectively). The sensitivity and specificity of these imaging tests were also similar when analysed by typical vs atypical histology. CONCLUSIONS: CT scan, FDG-PET and SRS showed similar performance in terms of nodal staging for pulmonary carcinoid. These findings suggest that additional nuclear imaging beyond CT scan is not required as long as a lymphadenectomy or nodal sampling is completed at resection

PS01.25: Large Cell Neuroendocrine Carcinoma of the Lung: Prognostic Factors of Survival and Recurrence After R0 Surgical Resection: Topic: Surgery

Background Large cell neuroendocrine carcinomas (LCNEC) represent approximately 3% of all lung cancers. Due to this rarity, little knowledge exists about their outcome, prognosis or optimal treatment strategy. The objective of this study is to evaluate the outcomes of patients undergoing lung resection for LCNEC to identify the factors affecting survival and recurrence to help refine the optimal treatment strategy. Methods We retrospectively reviewed 116 patients who underwent lung resection at 8 centers between 2000-2015. We excluded 18 patients: pNX(3), stage IV(5), R1-2(10). Univariate and multivariate analysis were performed to identify factors influencing disease-specific survival, overall survival and recurrence. The variables included age, gender, smoking habit, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, tumor location, tumor size, pT, pleura invasion, pN, pStage and neo/adjuvant treatments. Kaplan-Meier, Cox regression and ROC curve were used. Results A total of 98 patients (M/F:60/38) were analyzed with a median age of 66 years (IQR=58-72). Prior to resection, 11 (11%) received induction therapy. Re included pneumonectomy (8), bilobectomy (3), lobectomy (76) and sublobar (11) with an associated lymph node sampling (N=52, 55%) and lymphadenectomy (N=43, 45%). Adjuvant therapy was delivered in 28 (30%). Pathologic stages were I (N=40, 41%), II (N=33, 34%) and IIIA (N=25, 25%). Median follow-up was 62 (IQR=19-120) months. The 5-year disease-specific and overall survival rates were 51.6% and 42.7%. On univariate analysis, pT was associated with disease-specific and overall survival (p=0.011, p=0.028). Similarly pT was also associated on multivariate analysis with disease-specific and overall survival (p=0.044, p=0.034). The recurrence rate was 55% (2% local, 10% regional, 32% systemic, 11% not-specified). The median disease-free interval was 16 (IQR=6-80) months. Local-regional recurrence wasn\u2019t associated with any factor on univariate analysis. Systemic recurrence was correlated with tumor size (p=0.002), pT (p=0.003) and pStage (p=0.024) on univariate analysis. Tumor size was an independent prognostic factor of systemic recurrence on multivariate analysis (p=0.001) with a threshold value of 3 cm (AUC=0.712). The 5-year disease-free survival for systemic recurrence in tumors < 3 cm or 653 cm was 75.4% and 37.8% (p=0.001). The 5-year disease-specific survival was 56.7% and 47.3% (p=0.088). Conclusion Treatment of LCNEC with predominately surgical resection results in a respectable 5-year survival. However, a high proportion of systemic recurrence occurs. Tumors 653 cm have a higher rate of systemic recurrence and lower rate of survival suggesting that adjuvant chemotherapy may be indicated for completely resected LCNEC 653 cm

Large Cell Neuroendocrine Tumor Size \u3e3 cm Negatively Impacts Long-Term Outcomes After R0 Resection.

BACKGROUND: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. METHODS: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. RESULTS: Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and \u3e3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p \u3c 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively. CONCLUSIONS: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors \u3e3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC \u3e3 cm, even in the absence of nodal involvement

Improvement in TNM staging of pulmonary neuroendocrine tumors requires histology and regrouping of tumor size

Neuroendocrine tumors of the lung are currently staged with the 7th edition TNM non-small cell lung cancer staging system. This decision, based on data analysis without data on histology or disease-specific survival, makes its applicability limited. This study proposes a specific staging system for these tumors. METHODS: We retrospectively analyzed 510 consecutive patients (female/male, 313/197; median age, 61 years; interquartile range, 51-70) undergoing lung resection for a primary neuroendocrine tumor between 2000 and 2015 in 8 centers. Multivariable analysis was performed using a Cox proportional hazard model to identify factors associated with disease-specific survival. A new staging system was proposed on the basis of the results of this analysis. Kaplan-Meier disease-specific survival was analyzed by stage using the proposed and the 7th TNM staging system. RESULTS: Follow-up was completed in 490 of 510 patients at a median of 51 months (interquartile range, 18-99). Histology (G1-typical carcinoid vs G2-atypical carcinoid vs G3-large-cell neuroendocrine carcinoma) and pT were independently associated with survival, but pN was not. After regrouping histology and pT, we proposed the following staging system: IA (pT1-2G1), IB (pT3G1, pT1G2), IIA (pT4G1, pT2-3G2, pT1G3), IIB (pT4G2, pT2-3G3), and III (pT4G3). The 5-year survivals were 97.9%, 81.0%, 69.1%, 51.8%, and 0%, respectively. By using the 7th TNM, 5-year survivals were 95.0%, 92.3%, 67.7%, 70.9%, and 65.1% for stage IA, IB, IIA, IIB, and III, respectively. CONCLUSIONS: Incorporating histology and regrouping tumor stage create a unique neuroendocrine tumor staging system that seems to predict survival better than the 7th TNM classification