Factors contributing to the high prevalence of multidrug-resistance/Rifampicin-resistance in patients with tuberculosis: an epidemiological cross sectional and qualitative study from Khabarovsk krai region of Russia.

BACKGROUND: Growing prevalence of multidrug-resistant/Rifampicin-resistant tuberculosis (MDR/RR-TB; resistance to Isoniazid and Rifampicin/Isolated resistance to Rifampicin) is putting in jeopardy the WHO End TB strategy. This study aimed to identify factors contributing to the high prevalence of MDR/RR-TB in Khabarovsk krai region of Russia. METHODS: A cross-sectional retrospective study was conducted, analyzing clinical, demographic, and drug susceptibility testing data on 1440 patients. As a source of raw data, the national electronic TB surveillance system was used. Anonymous data was collected on every patient diagnosed with TB in all healthcare facilities of the region from January 2018 to December 2019. Only patients with proven excretion of m. tuberculosis were included in the study. Factors associated with MDR/RR-TB were identified through logistic regression analysis, in conjunction with in-depth interviews with eight patients, five healthcare managers and five doctors. FINDINGS: 2661 patients were identified with TB, 1440 were incorporated in the study based on inclusion criteria. Of these, 618 (42.9%) were identified with MDR/RR-TB. Patients with a history of imprisonment were 16.53 times (95% CI 5.37 to 50.88,) more likely to have MDR/RR-TB, whereas re-treatment patients were 2.82 times (95% CI 2.16 to 3.66) more likely to have MDR/RR-TB. Other influencing factors included presence of disability (AOR is 2.32, 95% CI 1.38 to 3.89), cavitary disease (AOR is 1.76, 95% CI 1.37 to 2.25), and retirement status (AOR 0.65, 95% CI 0.43 to 0.98, p = 0.042). Poor patient knowledge and understanding of the disease, progressive weariness of prolonged TB treatment, and inability hospitalize infectious patients without their consent were perceived by the interviewees as major influencing factors. CONCLUSIONS: Incarceration and treatment history, regardless of outcome, were identified as major factors influencing MDR/RR-TB prevalence. It is essential for the TB care system to eliminate legal loopholes, which deprive doctors of means to enforce quarantine procedures and epidemiological surveillance on infected patients, former and current inmates. Increasing people's awareness of TB, early detection and appropriate treatment of patients with TB are needed for successfully combating MDR/RR-TB.

Tropheryma whipplei as a Cause of Epidemic Fever, Senegal, 2010-2012.

The bacterium Tropheryma whipplei, which causes Whipple disease in humans, is commonly detected in the feces of persons in Africa. It is also associated with acute infections. We investigated the role of T. whipplei in febrile patients from 2 rural villages in Senegal. During June 2010-March 2012, we collected whole-blood finger-prick samples from 786 febrile and 385 healthy villagers. T. whipplei was detected in blood specimens from 36 (4.6%) of the 786 febrile patients and in 1 (0.25%) of the 385 apparently healthy persons. Of the 37 T. whipplei cases, 26 (70.2%) were detected in August 2010. Familial cases and a potential new genotype were observed. The patients' symptoms were mainly headache (68.9%) and cough (36.1%). Our findings suggest that T. whipplei is a cause of epidemic fever in Senegal.

The detection of vector-borne-disease-related DNA in human stool paves the way to large epidemiological studies.

The detection of Plasmodium spp. by the molecular analysis of human feces was reported to be comparable to detection in the blood. We believe that for epidemiological studies using molecular tools, it would be simpler to use feces, which are easier to obtain and require no training for their collection. Our aim was to evaluate the usefulness of feces for the detection of these pathogens towards developing a new tool for their surveillance. Between 2008 and 2010, 451 human fecal samples were collected in two Senegalese villages in which malaria and rickettsioses are endemic. Rickettsia and Plasmodium DNA were detected using quantitative PCR targeting Rickettsia of the spotted fever group, R. felis and Plasmodium spp. Two different sequences were systematically targeted for each pathogen. Twenty of the 451 fecal samples (4.4 %) were positive for Rickettsia spp., including 8 for R. felis. Inhabitants of Dielmo were more affected (18/230, 7.8 %; p = 0.0008) compared to those of Ndiop (2/221, 0.9 %). Children under 15 years of age were more often positive (19/285, 6.7 %) than were older children (1/166, 0.6 %; p = 0.005, odds ratio = 11.79). Only one sample was positive for Plasmodium spp. This prevalence is similar to that found in the blood of the Senegalese population reported previously. This preliminary report provides a proof of concept for the use of feces for detecting human pathogens, including microorganisms that do not cause gastroenteritis, in epidemiological studies.

Borrelia crocidurae infection in acutely febrile patients, Senegal.

As malaria cases in Africa decline, other causes of acute febrile illness are being explored. To determine incidence of Borrelia crocidurae infection during June 2010-October 2011, we collected 1,566 blood specimens from febrile patients in Senegal. Incidence was high (7.3%). New treatment strategies, possibly doxycycline, might be indicated for febrile patients.

Prevalence of Bartonella quintana in patients with fever and head lice from rural areas of Sine-Saloum, Senegal.

Trench fever is poorly known by the staff of health facilities that manage febrile patients in Senegal. Bartonella quintana DNA was identified in 5 of 274 (2%) febrile patients from two rural dispensaries and 2 of 71 (3%) head lice specimens collected from the same villages.

Common epidemiology of Rickettsia felis infection and malaria, Africa.

This study aimed to compare the epidemiology of Rickettsia felis infection and malaria in France, North Africa, and sub-Saharan Africa and to identify a common vector. Blood specimens from 3,122 febrile patients and from 500 nonfebrile persons were analyzed for R. felis and Plasmodium spp. We observed a significant linear trend (p<0.0001) of increasing risk for R. felis infection. The risks were lowest in France, Tunisia, and Algeria (1%), and highest in rural Senegal (15%). Co-infections with R. felis and Plasmodium spp. and occurrences of R. felis relapses or reinfections were identified. This study demonstrates a correlation between malaria and R. felis infection regarding geographic distribution, seasonality, asymptomatic infections, and a potential vector. R. felis infection should be suspected in these geographical areas where malaria is endemic. Doxycycline chemoprophylaxis against malaria in travelers to sub-Saharan Africa also protects against rickettsioses; thus, empirical treatment strategies for febrile illness for travelers and residents in sub-Saharan Africa may require reevaluation.

Vectorborne diseases in West Africa: geographic distribution and geospatial characteristics.

This paper provides an overview of the methods in which geographic information systems (GIS) and remote sensing (RS) technology have been used to visualise and analyse data related to vectorborne diseases (VBD) in West Africa and to discuss the potential for these approaches to be routinely included in future studies of VBDs. GIS/RS studies of diseases that are associated with a specific geographic landscape were reviewed, including malaria, human African trypanosomiasis, leishmaniasis, lymphatic filariasis, Loa loa filariasis, onchocerciasis, Rift Valley fever, dengue, yellow fever, borreliosis, rickettsioses, Buruli ulcer and Q fever. RS data and powerful spatial modelling methods improve our understanding of how environmental factors affect the vectors and transmission of VBDs. There is great potential for the use of GIS/RS technologies in the surveillance, prevention and control of vectorborne and other infectious diseases in West Africa.

Molecular evidence for the presence of Rickettsia Felis in the feces of wild-living African apes.

BACKGROUND: Rickettsia felis is a common emerging pathogen detected in mosquitoes in sub-Saharan Africa. We hypothesized that, as with malaria, great apes may be exposed to the infectious bite of infected mosquitoes and release R. felis DNA in their feces. METHODS: We conducted a study of 17 forest sites in Central Africa, testing 1,028 fecal samples from 313 chimpanzees, 430 gorillas and 285 bonobos. The presence of rickettsial DNA was investigated by specific quantitative real-time PCR. Positive results were confirmed by a second PCR using primers and a probe targeting a specific gene for R. felis. All positive samples were sequenced. RESULTS: Overall, 113 samples (11%) were positive for the Rickettsia-specific gltA gene, including 25 (22%) that were positive for R. felis. The citrate synthase (gltA) sequence and outer membrane protein A (ompA) sequence analysis indicated 99% identity at the nucleotide level to R. felis. The 88 other samples (78%) were negative using R. felis-specific qPCR and were compatible with R. felis-like organisms. CONCLUSION: For the first time, we detected R. felis in wild-living ape feces. This non invasive detection of human pathogens in endangered species opens up new possibilities in the molecular epidemiology and evolutionary analysis of infectious diseases, beside HIV and malaria.

Looking for Tropheryma whipplei source and reservoir in rural Senegal.

Tropheryma whipplei, the bacterium linked to Whipple's disease, is involved in acute infections and asymptomatic carriage. In rural Senegal, the prevalence of T. whipplei is generally high but is not homogeneous throughout households in the same village. We studied environmental samples collected in two Senegalese villages and conducted the survey to investigate the difference between households. Overall, the comparison between five households with very high T. whipplei prevalence and three households without any registered cases showed that the only difference was the presence of toilets in the latter (1/5 versus 3/3; P = 0.01423). Among the 1,002 environmental specimens (including domestic and synanthropic animals and dust sampled in households) tested for T. whipplei DNA, only four specimens were slightly positive. Humans are currently the predominant identified reservoir and source of T. whipplei in these populations. Limited access to toilets and exposure to human feces facilitate the fecal-oral transmission of T. whipplei.

The correlation of Q fever and Coxiella burnetii DNA in household environments in rural Senegal.

During 2008-2011, we tested 874 blood samples from febrile patients who had a fever >37.5°C, and 207 surface samples in households for Coxiella burnetii DNA in two rural Senegalese villages (Dielmo and Ndiop). Fisher's exact test and Spearman's correlation coefficient were used for statistical analysis. We identified four blood samples as positive for Coxiella burnetii DNA. The prevalence of Q fever in all tested samples was 0.46% in the two villages. C. burnetii DNA was also found in 7.5% of the dust samples in Ndiop, and in 0.9% in Dielmo; the prevalence in households was 22.6% in Ndiop and 2.6% in Dielmo. In Ndiop we found a weak correlation between positive environmental samples and the occurrence of the disease. Our findings show an association of environmental C. burnetii with human Q fever cases in a recently identified endemic area in rural Senegal.

Rickettsia species in African Anopheles mosquitoes.

BACKGROUND: There is higher rate of R. felis infection among febrile patients than in healthy people in Sub-Saharan Africa, predominantly in the rainy season. Mosquitoes possess a high vectorial capacity and, because of their abundance and aggressiveness, likely play a role in rickettsial epidemiology. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative and traditional PCR assays specific for Rickettsia genes detected rickettsial DNA in 13 of 848 (1.5%) Anopheles mosquitoes collected from Côte d'Ivoire, Gabon, and Senegal. R. felis was detected in one An. gambiae molecular form S mosquito collected from Kahin, Côte d'Ivoire (1/77, 1.3%). Additionally, a new Rickettsia genotype was detected in five An. gambiae molecular form S mosquitoes collected from Côte d'Ivoire (5/77, 6.5%) and one mosquito from Libreville, Gabon (1/88, 1.1%), as well as six An. melas (6/67, 9%) mosquitoes collected from Port Gentil, Gabon. A sequence analysis of the gltA, ompB, ompA and sca4 genes indicated that this new Rickettsia sp. is closely related to R. felis. No rickettsial DNA was detected from An. funestus, An. arabiensis, or An. gambiae molecular form M mosquitoes. Additionally, a BLAST analysis of the gltA sequence from the new Rickettsia sp. resulted in a 99.71% sequence similarity to a species (JQ674485) previously detected in a blood sample of a Senegalese patient with a fever from the Bandafassi village, Kedougou region. CONCLUSION: R. felis was detected for the first time in An. gambiae molecular form S, which represents the major African malaria vector. The discovery of R. felis, as well as a new Rickettsia species, in mosquitoes raises new issues with respect to African rickettsial epidemiology that need to be investigated, such as bacterial isolation, the degree of the vectorial capacity of mosquitoes, the animal reservoirs, and human pathogenicity.

Tropheryma whipplei: a common bacterium in rural Senegal.

BACKGROUND: Tropheryma whipplei is known as the cause of Whipple's disease, but it is also an emerging pathogen, detected in stool, that causes various chronic localized infections without histological digestive involvement and is associated with acute infections, including gastroenteritis and bacteremia. METHODS/PRINCIPAL FINDINGS: We conducted a study in 2008 and 2009 using 497 non-diarrheic and diarrheic stool samples, 370 saliva samples, 454 sera samples and 105 samples obtained from water samples in two rural Sine-Saloum villages (Dielmo and Ndiop) in Senegal. The presence of T. whipplei was investigated by using specific quantitative PCR. Genotyping was performed on positive samples. A serological analysis by western blotting was performed to determine the seroprevalence and to detect seroconversion. Overall, T. whipplei was identified in 31.2% of the stool samples (139/446) and 3.5% of the saliva samples (13/370) obtained from healthy subjects. The carriage in the stool specimens was significantly (p<10(-3)) higher in children who were between 0 and 4 years old (60/80, 75%) compared to samples obtained from individuals who were between 5 to 10 years old (36/119, 30.2%) or between 11 and 99 years old (43/247, 17.4%). The carriage in the stool was also significantly more common (p = 0.015) in subjects with diarrhea (25/51, 49%). We identified 22 genotypes, 16 of which were new. Only one genotype (#53) was common to both villages. Among the specific genotypes, one (#52) was epidemic in Dielmo (15/28, 53.4%, p<10(-3)) and another (#49) in Ndiop (27.6%, p = 0.002). The overall seroprevalence was estimated at 72.8% (291/400). Seroconversion was detected in 66.7% (18/27) of children for whom PCR became positive in stools between 2008 and 2009. CONCLUSIONS/SIGNIFICANCE: T. whipplei is a common bacterium in the Sine-Saloum area of rural Senegal that is contracted early in childhood. Epidemic genotypes suggest a human transmission of the bacterium.