Assessment of schistosomiasis and soil-transmitted helminths prevalence in school-aged children and opportunities for integration of control in local health services in Kwilu Province, the Democratic Republic of the Congo.

OBJECTIVE: To determine the prevalence of schistosomiasis (SCH) and soil-transmitted helminths (STH) in the Democratic Republic of Congo, and to assess the capacity of the local health centres for diagnosis and treatment. METHODS: Cross-sectional school-based survey in two health districts in the Province of Kwilu. We collected a stool and a urine sample for parasitological examination. Urine filtration and duplicate Kato-Katz thick smears were used for the diagnosis of SCH. Health centres were evaluated using a structured questionnaire. RESULTS: In total, 526 children participated in the study and the overall prevalence of Schistosoma mansoni infection was 8.9% (95% CI: 3.5-13.2) in both districts. The prevalence was higher in Mosango (11.7%; 95% CI: 8.9-14.8) than Yasa Bonga district (6.2%; 95% CI: 1.1-11.4). Urine filtration showed that Schistosoma haematobium infection was not present. The combined STH infection prevalence was 58.1% in both districts; hookworm infection was the most common STH found in 52.9% (95% CI: 29.3-62.4) of subjects, followed by Ascaris lumbricoides 9.3% (95% CI: 5.8-15.5) and Trichuris trichiura 2.1% (95% CI: 0.9-4.9). Mixed STH infections were observed as well as SCH-STH coinfection. CONCLUSION: Further mapping of both SCH and STH burden is needed, and coverage of preventive chemotherapy in school-aged children should be increased.

Risk Factors associated with defaulting from visceral leishmaniasis treatment: analysis under routine programme conditions in Bihar, India.

OBJECTIVE: To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. METHODS: Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. RESULTS: During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. CONCLUSION: Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates.

Fatal Chromobacterium violaceum bacteraemia in rural Bandundu, Democratic Republic of the Congo.

We describe the first case of bacteraemia caused by Chromobacterium violaceum in the Democratic Republic of the Congo. This diagnosis was made in an apparently healthy adult who was admitted to a rural hospital of the province of Bandundu with severe community-acquired sepsis. The patient developed multi-organ failure and died; to our knowledge, this is the first reported fatal case in an adult in Africa.

Integration of diagnosis and treatment of sleeping sickness in primary healthcare facilities in the Democratic Republic of the Congo.

BACKGROUND: Control of human African trypanosomiasis (HAT) in the Democratic Republic of Congo (DRC) has always been a vertical programme, although attempts at integration in general health services were made in recent years. Now that HAT prevalence is declining, the integration question becomes even more crucial. We studied the level of attainment of integration of HAT case detection and management in primary care centres in two high-prevalence districts in the province of Bandundu, DRC. METHODS: We visited all 43 first-line health centres of Mushie and Kwamouth districts, conducted structured interviews and inspected facilities using a standardised checklist. We focused on: availability of well trained staff - besides HAT, we also tested for knowledge on tuberculosis; availability of equipment, consumables and supplies; and utilisation of the services. RESULTS: All health centres were operating but most were poorly equipped, and attendance rates were very low. We observed a median of 14 outpatient consultations per facility (IQR 8-21) in the week prior to our visit, that is two patients per day. The staff had good knowledge on presenting symptoms, diagnosis and treatment of both HAT and tuberculosis. Nine centres were accredited by the national programme as HAT diagnosis and treatment centres, but the most sensitive diagnostic confirmation test, the mini-anion exchange centrifugation technique (mAECT), was not present in any. Although all nine were performing the CATT screening test, only two had the required cold chain in working order. CONCLUSION: In these high-prevalence districts in DRC, staff is well-acquainted with HAT but lack the tools required for an adequate diagnostic procedure. Attendance rates of these primary care centres are extremely low, making timely recognition of a resurgence of HAT unlikely in the current state of affairs.

[Buruli ulcer in the health districts of the Democratic Republic of Congo from 1950 to 2013: literature review and new distribution map]. / Ulcère de Buruli dans les zones de santé en République démocratique du Congo, de 1950 à 2013 : revue documentaire et nouvelle carte de distribution.

This paper describes the current distribution of cases of Buruli ulcer (BU) by highlighting health districts that are endemic and suspected to be endemic, based on the studies, surveys, and activity reports published from 1950 to 2013. We define as endemic any health district with BU patients positive by PCR, whether or not positive on a Ziehl-Neelsen (ZN) test, culture or histologic sample. A district is defined as suspected to be endemic when it is a historical BU area, has BU clinical cases and/or patients with positive ZN, but negative PCR. Of the 515 health districts in the DRC, 17 were found to be endemic (3%) and 26 suspected to be endemic (5%). In most cases, former focal areas, described before 1974, remain currently active. New focal points were found along the Kwango River in the province of Bandundu. We also discovered the extension of former BU focal areas to neighboring health districts in the provinces of Bas-Congo, Bandundu, and Maniema. The need for diagnostic confirmation by PCR appears to be a requirement and a priority, not only in all former historical focal areas but also in the health districts newly suspected to be endemic.

Bayesian meta-analysis of diagnostic tests allowing for imperfect reference standards.

There is an increasing interest in meta-analyses of rapid diagnostic tests (RDTs) for infectious diseases. To avoid spectrum bias, these meta-analyses should focus on phase IV studies performed in the target population. For many infectious diseases, these target populations attend primary health care centers in resource-constrained settings where it is difficult to perform gold standard diagnostic tests. As a consequence, phase IV diagnostic studies often use imperfect reference standards, which may result in biased meta-analyses of the diagnostic accuracy of novel RDTs. We extend the standard bivariate model for the meta-analysis of diagnostic studies to correct for differing and imperfect reference standards in the primary studies and to accommodate data from studies that try to overcome the absence of a true gold standard through the use of latent class analysis. Using Bayesian methods, improved estimates of sensitivity and specificity are possible, especially when prior information is available on the diagnostic accuracy of the reference test. In this analysis, the deviance information criterion can be used to detect conflicts between the prior information and observed data. When applying the model to a dataset of the diagnostic accuracy of an RDT for visceral leishmaniasis, the standard meta-analytic methods appeared to underestimate the specificity of the RDT.

Village health workers in Bihar, India: an untapped resource in the struggle against kala-azar.

INTRODUCTION: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent; important components of early case finding and treatment are entrusted to the primary health care system (PHC). In an earlier study in Bihar, India, we discovered some major shortcomings in implementation, in particular related to monitoring of treatment and treatment outcomes. These shortcomings could be addressed through involvement of village health workers. In the current study we assessed knowledge, attitude and practice of these village health workers in relation to VL. Main objective was to assess the feasibility of their involvement in VL control. METHODS: We obtained a list of auxiliary nurses/midwives and accredited social health activists for the highly endemic district of Muzaffarpur. We randomly sampled 100 auxiliary nurses and 100 activists, who were visited in their homes for an interview. Questions were asked on knowledge, attitude and practice related to visceral leishmaniasis and to tuberculosis. RESULTS: Auxiliary nurses and activists know the presenting symptoms of visceral leishmaniasis, they know how it is diagnosed but they are not aware of the recommended first-line treatment. Many are already involved in tuberculosis control and are very well aware of the treatment modalities of tuberculosis, but few are involved in control of visceral leishmaniasis control. They are well organised, have strong links to the primary healthcare system and are ready to get more involved in visceral leishmaniasis control. CONCLUSION: To ensure adequate monitoring of visceral leishmaniasis treatment and treatment outcomes, the control programme urgently needs to consider involving auxiliary nurses and activists.

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world's largest sleeping sickness control program.

OBJECTIVE: To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006-2008. METHODS: Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. RESULTS: Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post-treatment follow-up was very poor in both provinces; only 25% had undergone at least one post-treatment follow-up examination, <1% had undergone the required four follow-up examinations. Relapse rates among those presenting for follow-up were high in Kasai (18%) but low in Bandundu (0.3%). CONCLUSIONS: High relapse rates in Kasai and poor compliance with post-treatment follow-up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes.

Monitoring drug effectiveness in kala-azar in Bihar, India: cost and feasibility of periodic random surveys vs. a health service-based reporting system.

OBJECTIVE: In 2009, a random survey was conducted in Muzaffarpur district to document the clinical outcomes of visceral leishmaniasis patients (VL) treated by the public health care system in 2008, to assess the effectiveness of miltefosine against VL. We analysed the operational feasibility and cost of such periodic random surveys as compared with health facility-based routine monitoring. METHODS: A random sample of 150 patients was drawn from registers kept at Primary Health Care centres. Patient records were examined, and the patients were located at their residence. Patients and physicians were interviewed with the help of two specifically designed questionnaires by a team of one supervisor, one physician and one field worker. Costs incurred during this survey were properly documented, and vehicle log books maintained for analysis. RESULTS: Hundred and 39 (76.7%) of the patients could be located. Eleven patients were not traceable. Per patient, follow-up cost was US$ 15.51 and on average 2.27 patients could be visited per team-day. Human resource involvement constituted 75% of the total cost whereas involvement of physician costs 51% of the total cost. CONCLUSION: A random survey to document clinical outcomes is costly and labour intensive but gives probably the most accurate information on drug effectiveness. A health service-based retrospective cohort reporting system modelled on the monitoring system developed by tuberculosis programmes could be a better alternative. Involvement of community health workers in such monitoring would offer the additional advantage of treatment supervision and support.

Health care-seeking behaviour and diagnostic delays for Human African Trypanosomiasis in the Democratic Republic of the Congo.

OBJECTIVE: About half of the patients with Human African trypanosomiasis (HAT) reported in the Democratic Republic of the Congo (DRC) are currently detected by fixed health facilities and not by mobile teams. Given the recent policy to integrate HAT control into general health services, we studied health seeking behaviour in these spontaneously presenting patients. METHODS: We took a random sample from all patients diagnosed with a first-time HAT episode through passive case finding between 1 October 2008 and 30 September 2009 in the two most endemic provinces of the DRC. Patients were approached at their homes for a structured interview. We documented patient delay (i.e. time between onset of symptoms and contacting a health centre) and health system delay (i.e. time between first contact and correct diagnosis of HAT). RESULTS: Median patient delay was 4 months (IQR 1-10 months, n = 66); median health system delay was 3 months (IQR 0.5-11 months). Those first presenting to public health centres had a median systems delay of 7 months (IQR 2-14 months, n = 23). On median, patients were diagnosed upon the forth visit to a health facility (IQR 3rd-7th visit). CONCLUSIONS: Substantial patient as well as health system delays are incurred in HAT cases detected passively. Public health centres are performing poorly in the diagnostic work-up for HAT, mainly because HAT is a relatively rare disease with few and non-specific early symptoms. Integration of HAT diagnosis and treatment into general health services requires strong technical support and well-organized supervision and referral mechanisms.

Will visceral leishmaniasis be eliminated from Nepal? A review of recent (1994-2006) control efforts.

The Visceral Leishmaniasis (VL) control program in Nepal launched in 1993 includes provision of free diagnostic test, treatment along with vector control by indoor residual spraying. However, even after 14 years the disease is far from being controlled. Elimination of VL by 2015 has recently been identified as a regional priority with high level of political commitment. We analyzed the VL control effort in Nepal over the period 1994-2006 and tried to formulate recommendations for the VL elimination initiative. To document performance of the VL control program in Nepal we used literature review and a case study. First, we reviewed articles on VL in Nepal published in medical journals through Pubmed, ISI Web of Science, Google scholar and by hand searching. Secondly, the grey literature, mainly the reports on VL drafted by the Ministry of Health was reviewed for the period 1994-2006. Thirdly, a case study is presented to analyze the performance of the VL elimination program in a "pilot district", where the program was launched in 2006. There are only few studies available on VL in Nepal discussing the epidemiology, diagnosis, treatment, vector bionomics, human behavior and prevention. The review of the grey literature from 1994-2006 revealed that the VL incidence rate remained almost constant since 1993 despite the control efforts. The case study showed that there is a lack of trained human resources, laboratory facilities and treatment guidelines which is hindering the decentralization of the VL elimination program.

Socio-economic aspects of neglected diseases: sleeping sickness and visceral leishmaniasis.

Several tropical diseases that are essentially poverty-related have recently gained more attention under the label of 'neglected tropical diseases' or NTD. It is estimated that over 1000 million people currently suffer from one or more NTD. Here, the socio-economic aspects of two NTD - human African trypanosomiasis and human visceral leishmaniasis - are reviewed. Both of these diseases affect the poorest of the poor in endemic countries, cause considerable direct and indirect costs (even though the national control programmes tend to provide free care) and push affected households deeper into poverty.

Management of visceral leishmaniasis in rural primary health care services in Bihar, India.

OBJECTIVE: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent, with early diagnosis based on a rapid diagnostic test and treatment with the oral drug miltefosine as its main strategy. Several recent studies have signaled underreporting of VL cases in the region. Information on treatment outcomes is scanty. Our aim was to document VL case management by the primary health care services in India. METHODS: We took a random sample of all VL patients registered in rural primary health care (PHC) facilities of Muzaffarpur district, Bihar, India during 2008. Patients were traced at home for an interview and their records were reviewed. We recorded patient and doctor delay, treatment regimens, treatment outcomes and costs incurred by patients. RESULTS: We could review records of all 150 patients sampled and interview 139 patients or their guardian. Most patients (81%) had first presented to unqualified practitioners; median delay before reaching the appropriate primary healthcare facility was 40 days (IQR 31-59 days). Existing networks of village health workers were under-used. 48% of VL patients were treated with antimonials; 40% of those needed a second treatment course. Median direct expenditure by patients was 4000 rupees per episode (IQR 2695-5563 rupees), equivalent to almost 2 months of household income. CONCLUSION: In 2008 still critical flaws remained in VL case management in the primary health care services in Bihar: obsolete use of antimonials with high failure rates and long patient delay. To meet the target of the VL elimination, more active case detection strategies are needed, and village health worker networks could be more involved. Costs to patients remain an obstacle to early case finding.

Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.

OBJECTIVE: Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. METHODS: Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. RESULTS: We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. CONCLUSION: Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.

Development and evaluation of different PCR-based typing methods for discrimination of Leishmania donovani isolates from Nepal.

INTRODUCTION: Leishmania donovani, the causative agent of visceral leishmaniasis in the Indian subcontinent, has been reported to be genetically homogeneous. In order to support ongoing initiatives to eliminate the disease, highly discriminative tools are required for documenting the parasite population and dynamics. METHODS: Thirty-four clinical isolates of L. donovani from Nepal were analysed on the basis of size and restriction endonuclease polymorphisms of PCR amplicons from kinetoplast minicircle DNA, 5 nuclear microsatellites, and nuclear loci encoding glycoprotein 63, cysteine proteinase B, and hydrophilic acylated surface protein B. We present and validate a procedure allowing standardized analysis of kDNA fingerprint patterns. RESULTS: Our results show that parasites are best discriminated on the basis of kinetoplast minicircle DNA (14 genotypes) and 1 microsatellite defining 7 genotypes, while the remaining markers discriminated 2 groups or were monomorphic. Combination of all nuclear markers revealed 8 genotypes, while extension with kDNA data yielded 18 genotypes. CONCLUSION: We present tools that allow discrimination of closely related L. donovani strains circulating in the Terai region of Nepal. These can be used to study the micro-epidemiology of parasite populations, determine the geographical origin of infections, distinguish relapses from re-infection, and monitor the spread of particular variants.

Determinants of bednet ownership and use in visceral leishmaniasis-endemic areas of the Indian subcontinent.

OBJECTIVE: To document ownership and use of bednets with its determinants in the visceral leishmaniasis (VL)-endemic region where mainly non-insecticide impregnated nets are available through commercial channels, and bednets are being considered as a leishmaniasis vector control measure. METHODS: In August-September 2006, semi-structured household (HH) questionnaires and observation guides were used in a random sample of 1330 HHs in VL-endemic districts of India and Nepal to collect data on VL knowledge, HH socio-economic status, bednet ownership and use patterns. An asset index was constructed to allow wealth ranking of the HH. A binary logistic response General Estimating Equations model was fitted to evaluate the determinants of bednet ownership and use. RESULTS: The proportion of HHs with at least one bednet purchased on the commercial market was 81.5% in India and 70.2% in Nepal. The bednets were used in all seasons by 50.6% and 54.1% of the Indian and Nepalese HH owning a bed net. There was striking inequity in bednet ownership: only 38.3% of the poorest quintile in Nepal owned at least one net, compared to 89.7% of the wealthiest quintile. In India, the same trend was observed though somewhat less pronounced (73.6%vs. 93.7%). Multivariate analysis showed that poverty was an important independent predictor for not having a bednet in the HH [OR 5.39 (2.90-10.03)]. CONCLUSION: Given the inequity in commercial bednet ownership, free distribution of insecticide-treated bednets to the general population seems imperative to achieve a mass effect on vector density.

Clinical risk factors for therapeutic failure in kala-azar patients treated with pentavalent antimonials in Nepal.

Drug-related factors and parasite resistance have been implicated in the failure of pentavalent antimonials (Sb(v)) in the Indian subcontinent; however, little information is available on host-related factors. Parasitologically confirmed kala-azar patients, treatment naïve to Sb(v), were prospectively recruited at a referral hospital in Nepal and were treated under supervision with 30 doses of quality-assured sodium stibogluconate (SSG) 20mg/kg/day and followed for 12 months to assess cure. Analysis of risk factors for treatment failure was assessed in those receiving >or=25 doses and completing 12 months of follow-up. One hundred and ninety-eight cases were treated with SSG and the overall cure rate was 77.3% (153/198). Of the 181 cases who received >or=25 doses, 12-month follow-up data were obtained in 169, comprising 153 patients (90.5%) with definite cure and 16 (9.5%) treatment failures. In the final logistic regression model, increased failure to SSG was significantly associated with fever for >or=12 weeks [odds ratio (OR)=7.4], living in districts bordering the high SSG resistance zone in Bihar (OR=6.1), interruption of treatment (OR=4.3) and ambulatory treatment (OR=10.2). Early diagnosis and supervised treatment is of paramount importance to prevent treatment failures within the control programme.

Comparative study of kala-azar vector control measures in eastern Nepal.

This study was conducted to explore the most effective vector control tool among indoor residual spraying (IRS), long lasting insecticidal nets (LLINs) and ecological vector management (EVM) as a part of the regional visceral leishmaniasis elimination initiative. Alpha-cypermethrin as IRS, PermaNet as LLINs and plastering the inner walls of houses with lime as EVM were the interventions. One baseline and three follow-up entomological surveys were carried out in all arms using CDC miniature light traps (LT) and mouth aspirators. Comparisons were made between intervention arms and control arms with pre-intervention and post-intervention vector densities. Light traps were found more efficient in the collection of Phlebotomus argentipes in comparison with aspiration. Vector densities were significantly low in both IRS arm (p=0.009 in LT and p<0.001 in aspirator collections) and LLIN arm (p=0.019 in LT and p=0.023 in aspirator collections) in comparison with control arm. However, in EVM arm, there was no significant difference in P. argentipes sand fly density in comparison with control arm (p=0.785) in LT collections in follow-up surveys. Hence, IRS was found most effective control measure to decrease vector density. LLINs were also found effective and can be considered as a promising alternative vector control tool in VL elimination initiative.