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.

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.

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.

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.

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.

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.

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.

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.

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.

A new format of the CATT test for the detection of human African Trypanosomiasis, designed for use in peripheral health facilities.

OBJECTIVES: To test the reproducibility and thermostability of a new format of the Card-Agglutination Test for Trypanosomiasis (CATT) test for Human African Trypanosomiasis (HAT), designed for use at primary health care facility level in endemic countries. METHODS: A population of 4217 from highly endemic villages was screened using the existing format of the CATT test (CATT-R250) on whole blood. All those testing positive (220) and a random sample of negatives (555) were retested in the field with the new format (CATT-D10). Inter-format reproducibility was assessed by calculating kappa. All samples testing positive on whole blood with either method were further evaluated in Belgium by CATT titration of serum by two observers, using both old and new format. CATT-D10 test kits were incubated under four temperature regimens (4, 37, 45 degrees C and fluctuating) with regular assessments of reactivity over 18 months. RESULTS: Inter-format reproducibility of CATT-D10 vs. CATT-R250 on whole blood performed by laboratory technicians in the field was excellent with kappa values of 0.83-0.89. Both inter- and intra-format reproducibility assessed by CATT titration were excellent, with 96.5-100% of all differences observed falling within the limits of +/-1 titration step. After 18 months, reactivity of test kits incubated under all four temperature regimens was still well above the minimum threshold considered acceptable. CONCLUSION: The CATT-D10 is thermostable and can be used interchangeably with the old format of the CATT test. It is highly suitable for use in peripheral health facilities in HAT-endemic countries.

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.

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.

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.

Comparison of operational criteria for treatment outcome in gambiense human African trypanosomiasis.

OBJECTIVE: To develop a simple and standard operational decision tool for the diagnosis of relapse after treatment for human African trypanosomiasis (HAT), by evaluating the performance of several criteria currently used by HAT control programs and research projects. METHODS: We identified 10 different criteria for relapse, based on trypanosome presence and/or white blood cell count in cerebrospinal fluid, and compared their specificity, sensitivity and time to diagnosis on a data set containing 63 relapsed and 247 cured T.b. gambiense patients. RESULTS: At any time point, the criterion 'Trypanosomes present and/or a cerebrospinal white blood cell count > or =50/microl' allowed accurate and timely detection of HAT relapse, irrespective of disease stage. This criterion was 13-25% more sensitive (P < or = 0.013) than trypanosome detection alone and was >97% specific. Lumbar punctures at the end of treatment and at 3-month post-treatment provided limited clinical information. CONCLUSIONS: Adequate detection of relapse was possible with a simple criterion but these findings should be validated in a prospective study before adoption in clinical practice.

The poorest of the poor: a poverty appraisal of households affected by visceral leishmaniasis in Bihar, India.

OBJECTIVE: To provide data about wealth distribution in visceral leishmaniasis (VL)-affected communities compared to that of the general population of Bihar State, India. METHODS: After extensive disease risk mapping, 16 clusters with high VL transmission were selected in Bihar. An exhaustive census of all households in the clusters was conducted and socio-economic household characteristics were documented by questionnaire. Data on the general Bihar population taken from the National Family Health Survey of India were used for comparison. An asset index was developed based on Principal Components Analysis and the distribution of this asset index for the VL communities was compared with that of the general population of Bihar. RESULTS: 83% of households in communities with high VL attack rates belonged to the two lowest quintiles of the Bihar wealth distribution. All socio-economic indicators showed significantly lower wealth for those households. CONCLUSION: Visceral leishmaniasis clearly affects the poorest of the poor in India. They are most vulnerable, as this vector-born disease is linked to poor housing and unhealthy habitats. The disease leads the affected households to more destitution because of its impact on household income and wealth. Support for the present VL elimination initiative is important in the fight against poverty.

An outbreak of peritonitis caused by multidrug-resistant Salmonella Typhi in Kinshasa, Democratic Republic of Congo.

Between October 2004 and January 2005, 144 patients with peritonitis were admitted to the surgical wards of Kinshasa General Hospital and a few private city clinics. 63 patients (44%) underwent surgical intervention because of intestinal perforation consistent with typhoid fever; the case fatality rate was 53%. The majority of patients had received a course of first-line antibiotics such as chloramphenicol, ampicillin or co-trimoxazole before admission. On bacteriological investigation, Salmonella Typhi was isolated from the blood of 11 patients with peritonitis. The isolates were all resistant to ampicillin, chloramphenicol, tetracycline and co-trimoxazole, but sensitive to third-generation cephalosporins, quinolone (nalidixic acid, ciprofloxacine) and amoxicillin-clavulanic acid. Several factors contributed to the poor outcome of this disease including a) the use of inappropriate antibiotics, b) long delay in diagnosis, c) difficult access to health facilities. This is the first documented outbreak of typhoid fever caused by a multidrug-resistant S. Typhi in Kinshasa.

[Spatial variation of risk for pigs to contract trypanosomosis in farms situated in the peri-urban area of Kinshasa]. / Variation spatiale du risque pour les porcs de contracter la trypanosomose dans la zone périurbaine de Kinshasa.

In an effort to understand better the transmission risk as well for the animal African trypanosomosis (AAT) as for the human trypanosomosis (HAT) in the peri-urban zone of Kinshasa, a serologic study was carried out in local pig farms from 2003 to 2005. An indirect ELISA was used to detect the presence of trypanosome antibodies in 1,240 pigs originating from 404 farms. Seropositivity was recorded in 155 farms (38%), but varied considerably according to the district. In 6% of the farms TAA could be confirmed by parasitological examination. Trapping sites (n = 367) established in the neighbourhood of pig farms made it possible to capture 1,935 tsetse flies (Glossina fuscipes quanzensis). Among 562 dissected flies 23 were found to harbour trypanosomes resulting in an infection rate of 4.1%. In the majority of the districts the transmission risk for animal trypanosomosis anticipated from the apparent vector densities was corroborated by the serology. Zones with strong indications of local AAT transmission were identified in several quarters of three peri-urban districts of Kinshasa: Mount-Ngafula, Ngaliema and N'Sele. An intensification of tsetse control activities in those sites of increased transmission risk is essential.

Eflornithine is a cost-effective alternative to melarsoprol for the treatment of second-stage human West African trypanosomiasis in Caxito, Angola.

OBJECTIVE: To compare the cost-effectiveness of eflornithine and melarsoprol in the treatment of human African trypanosomiasis. METHOD: We used data from a Médecins Sans Frontières treatment project in Caxito, Angola to do a formal cost-effectiveness analysis, comparing the efficiency of an eflornithine-based approach with melarsoprol. Endpoints calculated were: cost per death avoided; incremental cost per additional life saved; cost per years of life lost (YLL) averted; incremental cost per YLL averted. Sensitivity analysis was done for all parameters for which uncertainty existed over the plausible range. We did an analysis with and without cost of trypanocidal drugs included. RESULTS: Effectiveness was 95.6% for melarsoprol and 98.7% for eflornithine. Cost/patient was 504.6 for melarsoprol and 552.3 for eflornithine, cost per life saved was 527.5 USD for melarsoprol and 559.8 USD for eflornithine without cost of trypanocidal drugs but it increases to 600.4 USD and 844.6 USD per patient saved and 627.6 USD and 856.1 USD per life saved when cost of trypanocidal drugs are included. Incremental cost-effectiveness ratio is 1596 USD per additional life saved and 58 USD per additional life year saved in the baseline scenario without cost of trypanocidal drugs but it increases to 8169 USD per additional life saved and 299 USD per additional life year saved if costs of trypanocidal drugs are included. CONCLUSION: Eflornithine saves more lives than melarsoprol, but melarsoprol is slightly more cost-effective. Switching from melarsoprol to eflornithine can be considered as a cost-effective option according to the WHO choice criteria.

Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent.

Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics.