Gundel Harms

Male Involvement in PMTCT Services in Mbeya Region, Tanzania

Throughout all stages of programmes for the prevention of mother-to-child-transmission of HIV (PMTCT), high dropout rates are common. Increased male involvement and couples’ joint HIV counselling/testing during antenatal care (ANC) seem crucial for improving PMTCT outcomes. Our study assessed male attitudes regarding partner involvement into ANC/PMTCT services in Mbeya Region, Tanzania, conducting 124 individual interviews and six focus group discussions. Almost all respondents generally supported PMTCT interventions. Mentioned barriers to ANC/PMTCT attendance included lacking information/knowledge, no time, neglected importance, the services representing a female responsibility, or fear of HIV-test results. Only few perceived couple HIV counselling/testing as disadvantageous. Among fathers who had refused previous ANC/PMTCT attendance, most had done so even though they were not perceiving a disadvantage about couple counselling/testing. The contradiction between men’s beneficial attitudes towards their involvement and low participation rates suggests that external barriers play a large role in this decision-making process and that partner’s needs should be more specifically addressed in ANC/PMTCT services.

Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-γ production.

Accumulating evidence points toward an antagonism between TH1 and TH2 focused immune responses decisive for the outcome of parasitic infections with leishmaniae. Interferon-gamma (IFN-gamma) and interleukin 4 (IL4), the principal cytokines involved in these pathways, as well as IgE and the IgG subclasses differentially modulated by these cytokines, were therefore assessed in 18 Brazilian patients with visceral leishmaniasis. The results are compared to those of a local control group. IL4 was detected in all patient sera but in only one control. Low concentrations of IFN-gamma where detectable in 50% of the Brazilian controls but in only two patients. While group medians of mitogen-induced in vitro synthesis of IL4 and IFN-gamma were similar, release of these lymphokines correlated inversely in patients (Spearmans rho = -0.84). Elevations of serum IgE complement the lymphokine data to indicate prominent TH2 type responses in clinical infections with Leishmania donovani.

Risk factors for treatment denial and loss to follow‐up in an antiretroviral treatment cohort in Kenya

Objectives:  To evaluate risk factors for treatment denial and loss to follow‐up in an antiretroviral treatment (ART) cohort in a rural African setting in western Kenya.

High Prevalence of Giardia duodenalis Assemblage B Infection and Association with Underweight in Rwandan Children

Background Giardia duodenalis is highly endemic in East Africa but its effects on child health, particularly of submicroscopic infections, i.e., those below the threshold of microscopy, and of genetic subgroups (assemblages), are not well understood. We aimed at addressing these questions and at examining epidemiological characteristics of G. duodenalis in southern highland Rwanda. Methodology/Principal Findings In 583 children <5 years of age from communities and health facilities, intestinal parasites were assessed by triplicate light microscopy and by PCR assays, and G. duodenalis assemblages were genotyped. Cluster effects of villages were taken into account in statistical analysis. The prevalence of G. duodenalis as detected by microscopy was 19.8% but 60.1% including PCR results. Prevalence differed with residence, increased with age, and was reduced by breastfeeding. In 492 community children without, with submicroscopic and with microscopic infection, underweight (weight-for-age z-score <−2 standard deviations) was observed in 19.7%, 22.1%, and 33.1%, respectively, and clinically assessed severe malnutrition in 4.5%, 9.5%, and 16.7%. Multivariate analysis identified microscopically detectable G. duodenalis infection as an independent predictor of underweight and clinically assessed severe malnutrition. Submicroscopic infection showed respective trends. Overall, G. duodenalis was not associated with gastrointestinal symptoms but assemblages A parasites (proportion, 13%) were increased among children with vomiting and abdominal pain. Conclusions/Significance The prevalence of G. duodenalis in high-endemicity areas may be greatly underestimated by light microscopy, particularly when only single stool samples are analysed. Children with submicroscopic infections show limited overt manifestation, but constitute unrecognized reservoirs of transmission. The predominance of assemblage B in Rwanda may be involved in the seemingly unimposing manifestation of G. duodenalis infection. However, the association with impaired child growth points to its actual relevance. Longitudinal studies considering abundant submicroscopic infections are needed to clarify the actual contribution of G. duodenalis to morbidity in areas of high endemicity.

Implementation research to support the initiative on the elimination of kala azar from Bangladesh, India and Nepal – the challenges for diagnosis and treatment

1 Institute of Medical Sciences, Banaras Hindu University, Varanasi, India 2 Parasitology Laboratory, ICDDR, Dhaka, Bangladesh 3 Koirala Institute of Health Sciences, Dharan, Nepal 4 Additional Director General, Indian Council of Medical Research, New Delhi, India 5 WHO/TDR, Geneva, Switzerland 6 Institute of Tropical Medicine, Antwerp, Belgium 7 Institute for OneWorld Health, Divonne, France 8 Deutsche Gesellschaft fuer Technische Zusammenarbeit, GTZ, Eschborn, Germany 9 Institute of Tropical Medicine, Charite Medical School, Berlin, Germany

Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania

Background Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania. Methods and Findings A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold. Conclusions Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis.

Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis.

This review addresses the question of whether the risk of developing mucosal leishmaniasis (ML) warrants systemic treatment in all patients with New World cutaneous leishmaniasis (CL) or whether local treatment might be an acceptable alternative. The risk of patients with New World CL developing ML after the initial infection has been the main argument for systemic treatment. However, this statement needs re-evaluation and consideration of all the available data. The putative benefit of preventing ML should outweigh the toxicity of systemic antileishmanial therapy. To assess the need for and risk of systemic treatment the following factors were reviewed: the incidence and prevalence of ML in endemic populations and in travellers; the severity of mucosal lesions; the efficacy of current options to treat ML; the toxicity and, to a lesser extent, the costs of systemic treatment; the risk of developing ML after local treatment; and the strengths and limitations of current estimates of the risk of developing ML in different situations. Local treatment might be considered as a valuable treatment option for travellers suffering from New World CL, provided that there are no risk factors for developing ML such as multiple lesions, big lesions (>4 cm(2)), localisation of the lesion on the head or neck, immunosuppression or acquisition of infection in the high Andean countries, notably Bolivia.

A Study in a Community in Brazil in Which Cutaneous Larva Migrans Is Endemic

BACKGROUND Cutaneous larva migrans (CLM) is a common but neglected parasitic skin disease in impoverished communities of the developing world. METHODS To describe the clinical features and the morbidity associated with CLM, active-case finding was performed during rainy and dry seasons in a rural community in the state of Alagoas, Northeast Brazil. RESULTS A total of 62 individuals received a diagnosis for CLM, and among them there were a total of 75 larval tracks. The number of tracks per person ranged from 1 to 3. Children <9 years old were affected significantly more often than other age groups (P<.001). Children had their lesions mainly on the buttocks, genitals, and hands, whereas in older patients, the majority of lesions were located on the feet. Twenty-four percent of the 75 lesions were superinfected. Bacterial superinfection was more common among children. All but 1 patient complained about itching, and 84% of the 62 patients complained about sleep disturbances. Itching was classified as being severe by 61% of patients. Approximately 40% of the 62 patients had attempted to treat their creeping eruption previously. Larvae moved forward 2.7 mm per day. There was a significant correlation between the length of the track and the duration of infestation ( rho =.53; P<.0001). CONCLUSIONS CLM is a common parasitic skin disease in this rural community, with different topographic patterns of lesions in children and adults. CLM is associated with considerable morbidity. The length of the track can be used to estimate the duration of infestation.

Prevalence and risk factors of malaria among children in southern highland Rwanda

BackgroundIncreased control has produced remarkable reductions of malaria in some parts of sub-Saharan Africa, including Rwanda. In the southern highlands, near the district capital of Butare (altitude, 1,768 m), a combined community-and facility-based survey on Plasmodium infection was conducted early in 2010.MethodsA total of 749 children below five years of age were examined including 545 randomly selected from 24 villages, 103 attending the health centre in charge, and 101 at the referral district hospital. Clinical, parasitological, haematological, and socio-economic data were collected.ResultsPlasmodium falciparum infection (mean multiplicity, 2.08) was identified by microscopy and PCR in 11.7% and 16.7%, respectively; 5.5% of the children had malaria. PCR-based P. falciparum prevalence ranged between 0 and 38.5% in the villages, and was 21.4% in the health centre, and 14.9% in the hospital. Independent predictors of infection included increasing age, low mid-upper arm circumference, absence of several household assets, reported recent intake of artemether-lumefantrine, and chloroquine in plasma, measured by ELISA. Self-reported bed net use (58%) reduced infection only in univariate analysis. In the communities, most infections were seemingly asymptomatic but anaemia was observed in 82% and 28% of children with and without parasitaemia, respectively, the effect increasing with parasite density, and significant also for submicroscopic infections.ConclusionsPlasmodium falciparum infection in the highlands surrounding Butare, Rwanda, is seen in one out of six children under five years of age. The abundance of seemingly asymptomatic infections in the community forms a reservoir for transmission in this epidemic-prone area. Risk factors suggestive of low socio-economic status and insufficient effectiveness of self-reported bed net use refer to areas of improvable intervention.

Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration

OBJECTIVES Nevirapine is widely used in the developing world for the prevention of mother-to-child transmission (PMTCT) of HIV. A single mutation in the HIV genome is sufficient to lead to significant nevirapine resistance. Persistence of low-level drug concentrations in body compartments can foster resistance formation. In this study, concentration-time courses of nevirapine after single-dose administration were analysed over an extended post-partum period. PATIENTS AND METHODS Breast milk and plasma samples of 62 HIV-positive Ugandan mother-child pairs who had received single-dose nevirapine were collected at delivery and 1, 2 and 6 weeks post-partum. Nevirapine concentrations were quantified by LC/tandem-mass-spectrometry using a quantification limit of 15 ng/mL, and a population pharmacokinetic (PK) analysis was performed. RESULTS Concentration-time profiles in breast milk, maternal plasma and child plasma showed similar shapes. At week 1, median nevirapine concentrations were 164 ng/mL in maternal plasma, 114 ng/mL in breast milk and 183 ng/mL in child plasma. The population PK model predicted nevirapine concentrations>10 ng/mL (IC50 for nevirapine) for 13 days in breast milk, 14 days in maternal plasma and 18 days in child plasma in 80% of the samples. CONCLUSIONS Nevirapine concentrations were present for 2-3 weeks in the three compartments. The concentrations are probably sufficiently high to protect most breastfed children from HIV transmission during the first 2 weeks. The long presence of slowly decreasing levels of nevirapine is likely to induce resistance formation. Post-natal addition of antiretrovirals for 1 week only, as recommended in the current PMTCT guidelines, will not suffice to avoid nevirapine resistance formation.