Collecting baseline information for national morbidity alleviation programs: different methods to estimate lymphatic filariasis morbidity prevalence.

The lymphatic filariasis elimination program aims not only to stop transmission, but also to alleviate morbidity. Although geographically limited morbidity projects exist, few have been implemented nationally. For advocacy and planning, the program coordinators need prevalence estimates that are currently rarely available. This article compares several approaches to estimate morbidity prevalence: (1) data routinely collected during mapping or sentinel site activities; (2) data collected during drug coverage surveys; and (3) alternative surveys. Data were collected in Plateau and Nasarawa States in Nigeria and in 6 districts in Togo. In both settings, we found that questionnaires seem to underestimate the morbidity prevalence compared with existing information collected through clinical examination. We suggest that program managers use the latter for advocacy and planning, but if not available, questionnaires to estimate morbidity prevalence can be added to existing surveys. Even though such data will most likely underestimate the real burden of disease, they can be useful in resource-limited settings.

No depletion of Wolbachia from Onchocerca volvulus after a short course of rifampin and/or azithromycin.

Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four treatment groups: rifampin, azithromycin, a combination of the two drugs, and controls (multivitamins). After five days of antibiotic treatment, all participants received a single dose of ivermectin on day 6. Nine months after treatment, the nodules were removed and the worms were examined. Skin snips to determine microfilariae were obtained at baseline and nine months. There were no significant differences between any of the treatment groups in the condition of the worms in the nodules, the presence of Wolbachia surface protein, or the number of microfilariae in skin. Short courses with these antibiotics will not clear Wolbachia from O. volvulus.

The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village.

We examined the epidemiology of kala-azar and asymptomatic leishmanial infection measured by serologic and leishmanin skin test results in a Bangladeshi community. In a subset, we measured serum retinol, zinc and C-reactive protein (CRP). Kala-azar and seroconversion incidence were 15.6 and 63.1 per 1,000 person-years, respectively. Proximity to a previous kala-azar case increased the likelihood of both kala-azar and asymptomatic infection. Bed net use protected against kala-azar (rate ratio = 0.35, P < 0.01), but not subclinical infection (rate ratio = 1.1, P = 0.82). Kala-azar patients were younger (P < 0.001) and reported lower red meat consumption (P < 0.01) than asymptomatic seropositive individuals. Retinol and zinc levels were lower in current kala-azar patients and those who later developed kala-azar compared with uninfected and asymptomatically infected subjects. The CRP levels were higher in kala-azar patients compared with the other two groups. Low red meat intake and poor zinc and retinol status may characterize a group at higher risk of symptomatic disease.

The reliability of anterior segment lesions as indicators of onchocercal eye disease in Guatemala.

World Health Organization certification criteria for onchocerciasis elimination use anterior segment eye lesion prevalence as an indicator of mass ivermectin treatment program success. Lesions either contain visible microfilaria (noninflammatory punctate keratitis [PK] or microfilariae in anterior chamber [MFAC]), or microfilaria obscured by inflammation (inflammatory PK). To assess the utility of these disease indicators, two experienced ophthalmologists independently examined persons from endemic (N = 325) and nonendemic (N = 348) Guatemalan communities. Thirty-six (11.1%) and nine (2.6%) persons from endemic and nonendemic areas respectively had lesions found by either ophthalmologist (prevalence ratio = 4.3, 95% CI 2.1-8.8, P < 0.001). All lesions in nonendemic areas were inflammatory PK in whom no persons were seropositive for onchocerciasis. Overall, observer agreement was moderate (Kappa = 0.49), and most (61%) discordance occurred with inflammatory PK lesions. Our findings suggest that inflammatory punctate keratitis is neither a specific nor a reliable indicator of onchocercal eye disease. Future prevalence surveys should rely upon noninflammatory lesions as disease indicators.

Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal study of visceral leishmaniasis in Bangladesh.

Annual leishmanin skin test (LST) surveys were conducted in a visceral leishmaniasis-endemic Bangladeshi community from 2002 through 2004, using Leishmania infantum antigen from the same manufacturer and batch. In 2002, 530 (35%) of 1,532 had positive LST results; the prevalence increased with increasing age. The LST result was positive in 24 (51%) of 47, 18 (72%) of 25, and 11 (85%) of 13 kala-azar patients treated in the previous 1-11, 12-23, and 24-35 months. A positive LST result in 2002 was associated with protection against subsequent kala-azar (P < 0.0001). In 2003-2004, decreased antigen sensitivity was observed. Among 686 participants, 34% were LST-positive in 2002, 29% in 2003, and 19% in 2004. Of 63 cured kala-azar patients, 70% were positive in 2002, 53% in 2003, and only 30% in 2004. Among 171 participants tested with both antigens, L. infantum study antigen sensitivity was 70% compared with L. amazonensis antigen. Our data underscore the need for better production, standardization, and documentation of sensitivity, potency, and stability of leishmanin antigens.

The economic impact of visceral leishmaniasis on households in Bangladesh.

OBJECTIVES: To explore current patterns of diagnosis and treatment, quantify household economic impact and identify household strategies to cover the costs of visceral leishmaniasis (VL) care in rural Bangladesh. METHOD: Structured interviews with 113 VL patients from 87 households documenting all provider visits and expenditures for health care for VL, and the ways in which the expenditures were covered. RESULTS: Patients paid a median of 7 visits to six different providers before beginning VL treatment. All visited the subdistrict government hospital at least once. While health care, including antileishmanial drug therapy, is officially available free of charge at government facilities, 79% of patients reported making informal payments for provider access, diagnostics and drug administration; only 14% of patients received their full drug course from this source. For the 58% of patients who purchased the full treatment course, drug cost constituted 34% of direct expenditure. Median direct expenditure for one VL patient was US$87 and median income lost was $40; median total expenditure was 1.2 times annual per capita income of our study population. Households employed multiple coping strategies to cover expenditures, most commonly sale or rental of assets (62%) and taking out loans (64%). CONCLUSIONS: Visceral leishmaniasis treatment causes a major economic burden in affected families. Control strategies for VL should facilitate timely, affordable diagnosis and treatment of patients to decrease the infection reservoir and to alleviate the economic burden of VL on households.

Risk factors for kala-azar in Bangladesh.

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3-45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15-44 within household; OR 3.2 95% CI 1.7-6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53-0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70-0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar.

Visceral leishmaniasis: consequences to women in a Bangladeshi community.

Visceral leishmaniasis (VL) or kala-azar (KA) affects the rural poor, causing significant morbidity and mortality. We examined the epidemiological and social impact of KA in an affected village in Bangladesh. A population-based survey of the village residents showed a case fatality rate of 14.7% among females and 5.3% among males. Before initiation of the study, female patients were ill longer than males before they received treatment. Future work needs to focus on understanding the implications of KA on women and to develop sustainable strategies for appropriate and timely access to treatment.

Increased endothelial cell density in the paracentral and peripheral regions of the human cornea.

PURPOSE: To systematically investigate the central, paracentral, and peripheral endothelial cell density (ECD) in normal human corneas. DESIGN: Observational case series and experimental study. METHODS: Noncontact specular microscopy was undertaken to determine the ECD of the central, paracentral (2.7 +/- 0.2 mm from center) and peripheral (4.7 +/- 0.2 mm from center) regions of the cornea of 48 normal eyes. The ECDs of central and peripheral regions were also determined with contact specular microscopy in 21 normal eyes and a group of 30 Optisol-GS eye bank corneas were evaluated with alizarin red stain. Histologic ECD of 13 Optisol-GS stored corneas were also determined. RESULTS: Paracentral and peripheral ECD measured with the noncontact specular microscope were 5.8% (P <.01) and 9.6% (P <.001) increased compared with central ECD. Superior peripheral ECD was increased compared with the other three peripheral quadrants (P <.05) and was 15.9% higher than central ECD. Contact specular microscopy showed an increase of 8.9% in the peripheral ECD from the center. Alizarin red stained corneas confirmed the specular microscopy numbers with a 9.2% increase in the paracentral region, and a 17.2% increase in the peripheral region. Histological cross sections of human corneas also showed a 22.9% increase in peripheral ECD compared with the central region. CONCLUSIONS: The human cornea has an increased ECD in the paracentral and peripheral regions of cornea compared with the central region. The superior peripheral region of the corneal endothelium has the largest increase in ECD. These data on normal endothelial cell distribution in the human cornea are especially significant as they relate to new surgical techniques and endothelial wound repair.

Visceral leishmaniasis: consequences of a neglected disease in a Bangladeshi community.

Visceral leishmaniasis, or kala azar (KA), affects the rural poor, causing significant morbidity and mortality. We examined the epidemiologic, social, and economic impact of KA in a village in Bangladesh. A population-based survey among 2,348 people demonstrated a KA incidence of 2% per year from 2000 to 2002, with a case-fatality rate of 19% among adult women, compared with 6-8% among other demographic groups. Kala azar cases were geographically clustered in certain sections of the village. Anti-leishmanial drug shortages and the high cost of diagnosis and treatment caused substantial emotional and economic hardship for affected families. Communities wanted to learn more about KA, and were willing to take collective action to confront the problems it causes. To decrease the KA burden in endemic areas, community efforts should be supplemented with effective treatment programs to ensure access to appropriate and affordable diagnosis and case management.