Frequency and distribution of neglected tropical diseases in Mozambique: a systematic review.

BACKGROUND: Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. MAIN TEXT: Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. CONCLUSIONS: This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.

Frequency and distribution of neglected tropical diseases in Mozambique: a systematic review

Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. Main text: Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: crosssectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.

Improvement in the determination of HIV-1 tropism using the V3 gene sequence and a combination of bioinformatic tools.

Assessment of HIV tropism using bioinformatic tools based on V3 sequences correlates poorly with results provided by phenotypic tropism assays, particularly for recognizing X4 viruses. This may represent an obstacle for the use of CCR5 antagonists. An algorithm combining several bioinformatic tools might improve the correlation with phenotypic tropism results. A total of 200 V3 sequences from HIV-1 subtype B, available in several databases with known phenotypic tropism results, were used to evaluate the sensitivity and specificity of seven different bioinformatic tools (PSSM, SVM, C4.5 decision tree generator and C4.5, PART, Charge Rule, and Geno2pheno). The best predictive bioinformatic tools were identified, and a model combining several of these was built. Using the 200 reference sequences, SVM and geno2-pheno showed the highest sensitivity for detecting X4 viruses (98.8% and 93.7%, respectively); however, their specificity was relatively low (62.5% and 86.6%, respectively). For R5 viruses, PSSM and C4.5 gave the same results and outperformed other bioinformatic tools (95.7% sensitivity, 82% specificity). When results from three out of these four tools were concordant, the sensitivity and specificity, taking as reference the results from phenotypic tropism assays, were over 90% in predicting either R5 or X4 viruses (AUC: 0.9701; 95% CI: 0.9358-0.9889). An algorithm combining four distinct bioinformatic tools (SVM, geno2pheno, PSSM and C4.5), improves the genotypic prediction of HIV tropism, and merits further evaluation, as it might prove useful as a screening strategy in clinical practice.

[Description of immunogens of Chlamydia pneumoniae recognized by serum of individuals with peripheral artery disease]. / Descripción de inmunógenos de Chlamydia pneumoniae reconocidos por el suero de sujetos con enfermedad arterial periférica.

BACKGROUND AND OBJECTIVE: The relationship between antibodies to C. pneumoniae and presence of the bacteria was studied in individuals with peripheral arterial disease. PATIENTS AND METHOD: An observational analytical, case-control study was performed in 118 patients (68 cases, 50 controls) to investigate immunoglobulin (Ig) G and A against C. pneumoniae in serum, using Western-blot (commercial and no commercial methods), ELISA and MIF; DNA of the bacteria in vascular tissue biopsy specimens was studied by polymerase chain reaction. RESULTS: Using commercial Western-blot, significant presence of IgG anti-39 kDa and anti-54 kDa was found in cases and was related to MIF results and C. pneumoniae DNA findings; IgA anti-LPS, anti-92 kDa and anti-Hsp60 kDa were also found and related to DNA presence. Using no commercial Western-blot, significant presence of 128.8 and 9.2 kDa bands for IgG was detected in cases and associated with DNA presence; 70.8, 58.9, 47.9, 47.5, 18.4, 12.1, 10.6, 8.1, and 7.6 kDa bands for IgG were found in cases; and DNA was present when 54.6 and 1.1 kDa bands for IgG and 79.4, 50.1, and 18.4 kDa bands for IgA were also detected. CONCLUSIONS: Using Western-blot, a greater serologic response was found against certain proteins of the bacteria in individuals with peripheral arterial disease. This may reflect an initial stage with presence of DNA and specific IgG. Subsequently, even in absence of the bacteria, an immunomediated disease may develop with presence of IgA and IgG.

Descripción de inmunógenos de Chlamydia pneumoniae reconocidos por el suero de sujetos con enfermedad arterial periférica / Description of immunogens of Chlamydia pneumoniae recognized by serum of individuals with peripheral artery disease

Fundamento y objetivo: Se estudian, en sujetos con enfermedad arterial periférica, los tipos de anticuerpos frente a Chlamydia pneumoniae y su relación con la presencia de la bacteria. Pacientes y método: Se ha realizado un estudio en 68 casos y 50 controles en los que se investigaron en suero las inmunoglobulinas (Ig) G y A frente a C. pneumoniae mediante Western-blot (comercial y no comercial), enzimoinmunoanálisis y microinmunofluorescencia (MIF), así como el ADN de la bacteria en biopsia de tejido vascular mediante reacción en cadena de la polimerasa. Resultados: Mediante Western-blot comercial se encontró, en los casos, una presencia significativa de IgG anti-39 kDa y anti-54 kDa, que se relacionaron con los resultados obtenidos mediante MIF y con la presencia de ADN de C. pneumoniae; así como de IgA antilipopolisacárido, anti-92 kDa y anti-Hsp60 kDa, que se relacionaron con la presencia de ADN. Mediante Western-blot no comercial destacó la presencia significativa, en los casos, de las bandas de 128,8 y 9,2 kDa para la IgG, que se asoció con la existencia de ADN; también se detectaron en los casos bandas de IgG de 70,8, 58,9, 47,9, 47,5, 18,4, 12,1, 10,6, 8,1 y 7,6 kDa; asimismo se detectó ADN cuando se observaron las bandas de 54,6 y 1,1 kDa de IgG, y las bandas de 79,4, 50,1 y 18,4 kDa de IgA. Conclusiones: En los sujetos con enfermedad arterial periférica se encontró una respuesta serológica, mediante Western-blot, más importante frente a determinadas proteínas de la bacteria. Esto podría reflejar una fase inicial con presencia de ADN e IgG específica. Posteriormente, aun en ausencia de la bacteria, podría existir una enfermedad inmunomediada con presencia de IgA e IgG

Background and objective: The relationship between antibodies to C. pneumoniae and presence of the bacteria was studied in individuals with peripheral arterial disease. Patients and method: An observational analytical, case-control study was performed in 118 patients (68 cases, 50 controls) to investigate immunoglobulin (Ig) G and A against C. pneumoniae in serum, using Western-blot (commercial and no commercial methods), ELISA and MIF; DNA of the bacteria in vascular tissue biopsy specimens was studied by polymerase chain reaction. Results: Using commercial Western-blot, significant presence of IgG anti-39 kDa and anti-54 kDa was found in cases and was related to MIF results and C. pneumoniae DNA findings; IgA anti-LPS, anti-92 kDa and anti-Hsp60 kDa were also found and related to DNA presence. Using no commercial Western-blot, significant presence of 128.8 and 9.2 kDa bands for IgG was detected in cases and associated with DNA presence; 70.8, 58.9, 47.9, 47.5, 18.4, 12.1, 10.6, 8.1, and 7.6 kDa bands for IgG were found in cases; and DNA was present when 54.6 and 1.1 kDa bands for IgG and 79.4, 50.1, and 18.4 kDa bands for IgA were also detected. Conclusions: Using Western-blot, a greater serologic response was found against certain proteins of the bacteria in individuals with peripheral arterial disease. This may reflect an initial stage with presence of DNA and specific IgG. Subsequently, even in absence of the bacteria, an immunomediated disease may develop with presence of IgA and IgG

[Relationship between the peripheral arterial occlusive disease and the infection by Chlamydophila pneumoniae]. / Relación entre la enfermedad arterial periférica oclusiva y la infección por Chlamydophila pneumoniae.

BACKGROUND AND OBJECTIVE: The relationship between peripheral arterial occlusive disease (PAOD) and Chlamydophila pneumoniae infection was studied by analyzing clinical samples from 95 patients with PAOD (cases) and 100 controls. PATIENTS AND METHOD: The following investigations were conducted: IgG and IgA against lipopolysaccharide (LPS) and against purified C. pneumoniae-specific antigens from elementary bodies (EB) with ELISA; anti-EB IgG, with MIF; C. pneumoniae DNA in arterial biopsy and peripheral blood leukocyte cells (PBLCs) with heminested PCR; LPS with ELISA; and bacteria culture in HEp-2 cells from arterial biopsy. RESULTS: The percentage of positive results in cases and controls groups for anti-LPS IgG was: 21% and 14%, respectively, with no differences; nor were there any differences with IgA (22 and 21%, respectively). However, differences were seen in the anti-EB IgG between cases (74% and 72%, for ELISA and MIF, respectively) and controls (31% and 34%). There were no differences in anti-EB IgA. Bacterial DNA was detected in 67% of atheromatous plaques (cases) vs. 12% of pudendal arteries (controls) (p = 0.0001). No C. pneumoniae DNA and LPS was detected in PBLCs and biopsic samples, respectively; and no C. pneumoniae strain could be recovered by cell culture from cases. CONCLUSIONS: On the basis of our results, PAOD is significantly associated with C. pneumoniae infection through the detection of anti-EB IgG from serum and bacterial DNA from arterial biopsy.

Relación entre la enfermedad arterial periférica oclusiva y la infección por Chlamydophila pneumoniae / Relationship between the peripheral arterial occlusive disease and the infection by Chlamydophila pneumoniae

FUNDAMENTO Y OBJETIVO: Estudiar la relación entre la enfermedad arterial periférica oclusiva y la infección por Chlamydophila pneumoniae a través del estudio de muestras clínicas de 95 enfermos (casos) y 100 controles. PACIENTES Y MÉTODO: Se investigaron mediante enzimoinmunoanálisis las inmunoglobulinas (Ig) G y A frente al lipopolisacárido (LPS) y antígenos específicos de C. pneumoniae presentes en cuerpos elementales (CE) purificados; mediante microinmunofluorescencia la IgG anti-CE; mediante reacción en cadena de la polimerasa semianidada, el ADN de C. pneumoniae en biopsias arteriales y leucocitos de sangre periférica; mediante enzimoinmunoanálisis el LPS, y la recuperación de la bacteria en células Hep-2 desde biopsias arteriales. RESULTADOS: Los valores obtenidos para la IgG anti-LPS en los grupos de casos y controles fueron del 21 y el 14 por ciento, respectivamente, sin diferencias significativas; tampoco la hubo para la IgA (el 22 y el 21 por ciento, respectivamente). Sí se encontraron diferencias para la IgG anti-CE entre los casos (el 74 y el 72 por ciento, para el enzimoinmunoanálisis y la microinmunofluorescencia, respectivamente) y los controles (el 31 y el 34 por ciento). No hubo diferencias para la IgA anti-CE. El ADN de la bacteria se detectó en el 67 por ciento de las placas de ateroma (casos) y en el 12 por ciento de las arterias pudendas (controles) (p = 0,0001). No se detectaron ADN y LPS de C. pneumoniae en los leucocitos y biopsias arteriales, respectivamente. No se pudo recuperar la bacteria mediante cultivo en el grupo de casos. CONCLUSIONES: Nuestros resultados asocian de manera significativa la enfermedad arterial periférica oclusiva con la infección por C. pneumoniae a través de la presencia de la IgG anti-CE en suero y el ADN de la bacteria en biopsia arterial (AU)

Genomic, serologic, and clinical case-control study of Chlamydia pneumoniae and peripheral artery occlusive disease.

OBJECTIVES: Chlamydia pneumoniae has been related to atherosclerotic disease in both seroepidemiologic and genomic studies. We performed a case-control study to determine seropositivity and DNA detection in arteries of patients with peripheral artery occlusive disease and of healthy subjects. METHODS: The study included 64 patients with peripheral artery occlusive disease, and 50 control subjects who underwent varicose vein surgery, matched to the patient group for age, sex, and tobacco use. The fibrinogen level in all study subjects was measured as a marker of inflammation. Blood samples were taken from all subjects for determination of immunoglobulin (Ig) G elementary bodies (EB) against C pneumoniae with microimmunofluorescence (MIF) and enzyme-linked immunosorbent assay (ELISA), and of IgA EB with ELISA. The cutoff titers were 1:32 for MIF and 1.1 for ELISA. Biopsy specimens of arterial atheromatous plaque were obtained from patients, and of pudendal artery and saphenous vein from control subjects, and were studied with hemi-nested polymerase chain reaction. RESULTS: There were no differences in fibrinogen level between patients and controls. The prevalence of IgG anti-EB with MIF was 78% in patients and 24% in control subjects (P =.0001; odds ratio [OR], 11.3; 95% confidence interval [CI], 4.7-27.2). Prevalence of IgG anti-EB with ELISA was 75% in patients and 16% in control subjects (P =.0001; OR, 15.7; 95% CI, 6.1-40). There were no differences in IgA anti-EB titers. Bacterial DNA was detected in 67% of atheromatous plaques versus 12% of pudendal arteries (P =.0001) and 4% of saphenous veins. A weak correlation was found between seropositivity and the presence of intravascular DNA. CONCLUSIONS: Our results support the hypothesis that C pneumoniae is related to the pathogenesis of atherosclerotic peripheral artery occlusive disease. CLINICAL RELEVANCE: This study explored the infectious hypothesis in the context of the pathogenesis of atherosclerosis. This hypothesis has been supported by findings that certain infectious agents can cause or accelerate the course of diseases in which the possibility of a microbial cause was not previously proposed, as in the case of peptic ulcer and spongiform encephalopathy. The present study demonstrated the presence of Chlamydia pneumoniae and seropositivity in atheromatous plaques in patients with peripheral artery occlusive disease. These results contribute to a body of research that is opening up the possibility of treating atherosclerotic disease with antibiotic agents, and preventing it with immunization.