Determinants of Visceral Leishmaniasis: A Case-Control Study in Gedaref State,Sudan

Background

Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital’s catchment area, Gedaref State, Sudan.

Methods

From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire.

Results

Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard’s immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants.

Discussion and conclusion

Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures.     

Accelerated Active Case Detection of Visceral Leishmaniasis Patients in Endemic Villages of Bangladesh

Background

The visceral leishmaniasis (VL) elimination program in Bangladesh is in its attack phase. The primary goal of this phase is to decrease the burden of VL as much as possible. Active case detection (ACD) by the fever camp method and an approach using past VL cases in the last 6–12 months have been found useful for detection of VL patients in the community. We aimed to explore the yield of Accelerated Active Case Detection (AACD) of non-self reporting VL as well as the factors that are associated with non-self reporting to hospitals in endemic communities of Bangladesh.

Methods

Our study was conducted in the Trishal sub-district of Mymensingh, a highly VL endemic region of Bangladesh. We used a two-stage sampling strategy from 12 VL endemic unions of Trishal. Two villages from each union were selected at random. We looked for VL patients who had self-reported to the hospital and were under treatment from these villages. Then we conducted AACD for VL cases in those villages using house-to-house visit. Suspected VL cases were referred to the Trishal hospital where diagnosis and treatment of VL was done following National Guidelines for VL case management. We collected socio-demographic information from patients or a patient guardian using a structured questionnaire.

Results

The total number of VL cases was 51. Nineteen of 51 (37.3%) were identified by AACD. Poverty, female gender and poor knowledge about VL were independent factors associated with non self-reporting to the hospital.

Conclusion

Our primary finding is that AACD is a useful method for early detection of VL cases that would otherwise go unreported to the hospital in later stage due to poverty, poor knowledge about VL and gender inequity. We recommend that the National VL Program should consider AACD to strengthen its early VL case detection strategy.     

Impact of ASHA Training on Active Case Detection of Visceral Leishmaniasis in Bihar,India

Background

One of the major challenges for management of visceral leishmaniasis (VL) is early diagnosis of cases to improve treatment outcome and reduce transmission. We have therefore investigated active case detection of VL with the help of accredited social health activists (ASHA). ASHAs are women who live in the community and receive performance-based incentives for overseeing maternal and other health-related issues in their village.

Methods and Principal Finding

Through conducting interviews with 400 randomly selected ASHAs from four primary health care centers (PHCs), it was observed that their level of knowledge about visceral leishmaniasis (VL) regarding transmission, diagnosis, and treatment was limited. The baseline data indicated that less than 10% of VL cases seeking treatment at the PHCs were referred by ASHAs. To increase the knowledge and the referral rate of VL cases by ASHAs, training sessions were carried out during the monthly ASHA meetings at their respective PHCs. Following a single training session, the referral rate increased from less than 10% to over 27% and the overall knowledge about VL substantially improved. It was not possible, however, to demonstrate that ASHA training reduced the time that individuals had fever before treatment at the PHC.

Conclusions

Training ASHAs to identify VL cases in villages for early diagnosis and treatment at the local PHC is feasible and should be undertaken routinely to improve knowledge about VL.     

Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial

Background

Visceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages.

Methods

A cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial—three intervention and three control clusters in both India and Nepal—were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration.

Findings

A random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%–42.5%) as measured by means of LTs.

Interpretation

The ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program.

Trial registration

ClinicalTrials.gov CT-2005-015374     

Latent Infection with Leishmania donovani in Highly Endemic Villages in Bihar,India

Introduction

Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4–10 to 1. We describe patterns of markers of Leishmania donovani infection and clinical VL in relation to age in Bihar, India.

Methods

We selected eleven villages highly endemic for Leishmania donovani. During a 1-year interval we conducted two house to house surveys during which we collected blood samples on filter paper from all consenting individuals aged 2 years and above. Samples were tested for anti-leishmania serology by Direct Agglutination Test (DAT) and rK39 ELISA. Data collected during the surveys included information on episodes of clinical VL among study participants.

Results

We enrolled 13,163 persons; 6.2% were reactive to DAT and 5.9% to rK39. Agreement between the tests was weak (kappa = 0.30). Among those who were negative on both tests at baseline, 3.6% had converted to sero-positive on either of the two tests one year later. Proportions of sero-positives and sero-converters increased steadily with age. Clinical VL occurred mainly among children and young adults (median age 19 years).

Discussion

Although infection with L. donovani is assumed to be permanent, serological markers revert to negative. Most VL cases occur at younger ages, yet we observed a steady increase with age in the frequency of sero-positivity and sero-conversion. Our findings can be explained by a boosting effect upon repeated exposure to the parasite or by intermittent release of parasites in infected subjects from safe target cells. A certain proportion of sero-negative subjects could have been infected but below the threshold of antibody abundance for our serologic testing.     

Incidence and Associated Factors of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Background

A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale.

Methods

HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis.

Results

The overall prevalence of HIV RNA ≥1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL.

Conclusions

The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.     

Incidence and Predictors of Adolescent's Early Sexual Debut after Three Decades of HIV Interventions in Tanzania: A Time to Debut Analysis

Purpose

To determine the incidence and predictors of adolescent’s early sexual debut after three decades of HIV interventions in Tanzania.

Methods

In a cross-section study of adolescents aged 16–19 residing in Morogoro Municipality, information on socio-demographic, parental-and-peer communication, and sexual behaviors were collected. Cox-regression analysis was used to examine predictors of time to sexual debut.

Results

A total of 316 adolescents with mean age of 17.5±0.9 were recruited. Half (48.7%) of adolescent were sexually active with mean age at sexual debut of 14.6±2.3. Of these, 57.8% had sex before their 15^th birthday with incidence of early sexual debut of 17.4/1000 person-years at risk. Adolescent family characteristics, peer pressure, alcohol use, parental and peer communication were key predictors of early sexual debut.

Conclusion

Parental and peer communication strategies works calling for efforts to increase its scope to reach all adolescents alongside promoting family stability and reducing adolescent alcohol consumption.     

Relative Risk of Visceral Leishmaniasis in Brazil: A Spatial Analysis in Urban Area

Background

Visceral leishmaniasis (VL) is a vector-borne disease whose factors involved in transmission are poorly understood, especially in more urban and densely populated counties. In Brazil, the VL urbanization is a challenge for the control program. The goals were to identify the greater risk areas for human VL and the risk factors involved in transmission.

Methodology

This is an ecological study on the relative risk of human VL. Spatial units of analysis were the coverage areas of the Basic Health Units (146 small-areas) of Belo Horizonte, Minas Gerais State, Brazil. Human VL cases, from 2007 to 2009 (n = 412), were obtained in the Brazilian Reportable Disease Information System. Bayesian approach was used to model the relative risk of VL including potential risk factors involved in transmission (canine infection, socioeconomic and environmental features) and to identify the small-areas of greater risk to human VL.

Principal Findings

The relative risk of VL was shown to be correlated with income, education, and the number of infected dogs per inhabitants. The estimates of relative risk of VL were higher than 1.0 in 54% of the areas (79/146). The spatial modeling highlighted 14 areas with the highest relative risk of VL and 12 of them are concentrated in the northern region of the city.

Conclusions

The spatial analysis used in this study is useful for the identification of small-areas according to risk of human VL and presents operational applicability in control and surveillance program in an urban environment with an unequal spatial distribution of the disease. Thus the frequent monitoring of relative risk of human VL in small-areas is important to direct and prioritize the actions of the control program in urban environment, especially in big cities.     

Predictors of visceral leishmaniasis relapse in HIV-infected patients: a systematic review

Background and Objectives

Visceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmania-endemic areas. Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses, the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-infected patients. This work is a systematic review of previous studies that have described predictors of VL relapse in HIV-infected patients.

Review Methods

We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials. Studies were selected if they included HIV-infected individuals with a VL diagnosis and patient follow-up after the leishmaniasis treatment with an analysis of the clearly defined outcome of prediction of relapse.

Results

Eighteen out 178 studies satisfied the specified inclusion criteria. Most patients were males between 30 and 40 years of age, and HIV transmission was primarily via intravenous drug use. Previous VL episodes were identified as risk factors for relapse in 3 studies. Two studies found that baseline CD4+ T cell count above 100 cells/mL was associated with a decreased relapse rate. The observation of an increase in CD4+ T cells at patient follow-up was associated with protection from relapse in 5 of 7 studies. Meta-analysis of all studies assessing secondary prophylaxis showed significant reduction of VL relapse rate following prophylaxis. None of the five observational studies evaluating the impact of highly active antiretroviral therapy use found a reduction in the risk of VL relapse upon patient follow-up.

Conclusion

Some predictors of VL relapse could be identified: a) the absence of an increase in CD4+ cells at follow-up; b) lack of secondary prophylaxis; and c) previous history of VL relapse. CD4+ counts below 100 cells/mL at the time of primary VL diagnosis may also be a predictive factor for VL relapse.     

Modeling the Cost-Effectiveness of the Integrated Disease Surveillance and Response (IDSR) System: Meningitis in Burkina Faso

Background

Effective surveillance for infectious diseases is an essential component of public health. There are few studies estimating the cost-effectiveness of starting or improving disease surveillance. We present a cost-effectiveness analysis the Integrated Disease Surveillance and Response (IDSR) strategy in Africa.

Methodology/Principal Findings

To assess the impact of the IDSR in Africa, we used pre- and post- IDSR meningococcal meningitis surveillance data from Burkina Faso (1996–2002 and 2003–2007). IDSR implementation was correlated with a median reduction of 2 weeks to peak of outbreaks (25^th percentile 1 week; 75^th percentile 4 weeks). IDSR was also correlated with a reduction of 43 meningitis cases per 100,000 (25^th–40: 75^th-129). Assuming the correlations between reductions in time to peak of outbreaks and cases are related, the cost-effectiveness of IDSR was $23 per case averted (25^th-$30; 75^th - cost saving), and $98 per meningitis-related death averted (25^th-$140: 75^th – cost saving).

Conclusions/Significance

We cannot absolutely claim that the measured differences were due to IDSR. We believe, however, that it is reasonable to claim that IDSR can improve the cost-effectiveness of public health surveillance.     

Patients with Blepharitis Are at Elevated Risk of Anxiety and Depression

Purpose

Population-based cohort study on the risk of anxiety and depression in patients with blepharitis is limited. This study evaluated whether blepharitis patients are at a higher risk of anxiety and depression.

Design

A retrospective cohort study.

Methods

We used the universal insurance claims data from 1997 to 2010 in Taiwan to identify annually patients with newly diagnosed blepharitis (N = 9764) and without the disease (N = 39056). Incidences, rate ratios (IRR) and hazard ratios (HR) of anxiety and depression were measured for both cohorts by baseline demographic characteristics and comorbidities until the end of 2010.

Results

Compared with the non-blepharitis cohort, the blepharitis cohort had higher incidence of anxiety (15.9 vs. 9.5 per 1000 person-years), with an adjusted HR of 1.58 (95% confidence interval (CI) = 1.46–1.70). The incidence of depression was also higher in the blepharitis cohort (7.66 vs. 5.05 per 1000 person-years), with an adjusted HR of 1.42 (95% CI = 1.28–1.58). The blepharitis cohort to the non-blepharitis cohort IRR decreased from 1.73 in the first quartile to 1.32 in the 4^th quartile for anxiety, and from 1.67 to 1.29 for depression.

Conclusions

Patients with blepharitis are at elevated risks of anxiety and depression. The risk is higher in earlier period after the diagnosis of blepharitis, and declines by time, but remains significantly higher for those with blepharitis than those without blepharitis.     

Strong Association between Serological Status and Probability of Progression to Clinical Visceral Leishmaniasis in Prospective Cohort Studies in India and Nepal

Introduction

Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4–10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers.

Methods

We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified.

Results

We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers.

Discussion

There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies.     

The Household Costs of Visceral Leishmaniasis Care in South-eastern Nepal

Background and objectives

Visceral leishmaniasis (VL) is an important public health problem in south-eastern Nepal affecting very poor rural communities. Since 2005, Nepal is involved in a regional initiative to eliminate VL. This study assessed the economic impact of VL on households and examined whether the intensified VL control efforts induced by the government resulted in a decrease in household costs.

Methods

Between August and September 2010, a household survey was conducted among 168 patients that had been treated for VL within 12 months prior to the survey in five districts in south-eastern Nepal. We collected data on health-seeking behaviour, direct and indirect costs and coping strategies.

Results

The median total cost of one episode of VL was US$ 165 or 11% of annual household income. The median delay between the onset of symptoms and presentation to a qualified provider was 25 days. Once the patient presented to a qualified provider, the delay to correct diagnosis was minimal (median 3 days). Direct and indirect costs (income losses) represented 47% and 53% of total costs respectively. Households used multiple strategies to cope with the cost of illness, mainly mobilizing cash/savings (71%) or taking a loan (56%).

Conclusions

The provision of free VL diagnosis and drugs by the Nepalese control programme has been an important policy measure to reduce the cost of VL to households. But despite the free VL drugs, the economic burden is still important for households. More effort should be put into reducing indirect costs, in particular the length of treatment, and preventing the transmission of VL through vector control.     

Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS

Background

The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.

Methods and Findings

Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56–3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders.

Conclusions

In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.     

Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial

Background

Visceral leishmaniasis is the world'' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial.

Methods

As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention.

Results

A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi.

Conclusions

This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions.     

CD4 dynamics over a 15 year-period among HIV controllers enrolled in the ANRS French observatory

Background

There are few large published studies of HIV controllers with long-term undetectable viral load (VL). We describe the characteristics and outcomes of 81 French HIV controllers.

Methods and Results

HIV controllers were defined as asymptomatic, antiretroviral-naïve persons infected ≥10 years previously, with HIV-RNA <400 copies/mL in >90% of plasma samples. All available CD4 and VL values were collected at enrolment. Mixed-effect linear models were used to analyze CD4 cell count slopes since diagnosis. HIV controllers represented 0.31% of all patients managed in French hospitals. Patients infected through intravenous drug use were overrepresented (31%) and homosexual men were underrepresented (26% of men) relative to the ANRS SEROCO cohort of subjects diagnosed during the same period. HIV controllers whose VL values were always below the detection limit of the assays were compared with those who had rare “blips” (<50% of VL values above the detection limit) or frequent blips (>50% of VL values above the detection limit). Estimated CD4 cell counts at HIV diagnosis were similar in the three groups. CD4 cell counts remained stable after HIV diagnosis in the “no blip” group, while they fell significantly in the two other groups (−0.26√CD4 and −0.28√CD4/mm³/year in the rare and frequent blip groups, respectively). No clinical, immunological or virological progression was observed in the no blip group, while 3 immunological and/or virological events and 4 cancers were observed in the blip subgroups.

Conclusions

Viral blips in HIV controllers are associated with a significant decline in CD4 T cells and may be associated with an increased risk of pathological events, possibly owing to chronic inflammation/immune activation.     

Epidemiological features of infantile hypertrophic pyloric stenosis in Taiwanese children: a Nation-Wide Analysis of Cases during 1997-2007

Objective

To describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children.

Materials and Methods

We reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007.

Results

A total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8^th through 10^thweeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1±2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28±7.10 days.

Conclusions

The incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed.     

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

Background

While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis (VL) by 2015, its control in other regions seems fraught with difficulties. Is there a scope for more effective VL control in the Americas where transmission is zoonotic? We reviewed the evidence on VL control strategies in Latin America—diagnosis, treatment, veterinary interventions, vector control—with respect to entomological and clinical outcomes.

Methodology/Principal Findings

We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials, from 1960 to November 2008 and references of selected articles. Intervention trials as well as observational studies that evaluated control strategies of VL in the Americas were included. While the use of rapid diagnostic tests for VL diagnosis seems well established, there is a striking lack of evidence from clinical trials for drug therapy and few well designed intervention studies for control of vectors or canine reservoirs.

Conclusion

Elimination of zoonotic VL in the Americas does not seem a realistic goal at this point given the lack of political commitment, gaps in scientific knowledge, and the weakness of case management and surveillance systems. Research priorities and current strategies should be reviewed with the aim of achieving better VL control.     

Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends

Background

Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized.

Methods

We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors.

Results

We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade ≥3 vs0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade ≥3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (−3.4%, 28.5%)) and a downward trend in deaths (APC = −18.1% (−22.5%, −13.4%)).

Conclusions

Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.