2018年 · 第07卷第01期

Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from antimonials to nonantimonials, and some of these have been used extensively in clinical treatment. With the exception of a few drugs, such as oxamniquine and metrifonate, most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy. Although oxamniquine and metrifonate have been used for schistosomiasis control, they are only effective against Schistosoma mansoni and S. haematobium, respectively. Currently, praziquantel is the only drug used for treatment of all five species of human schistosomes. In this review, the pharmacological and immunological effects of praziquantel against S. japonicum are summarized and discussed.

From the end of the 1970s until the 2000s, scientists have conducted a series of experimental studies on the effects of praziquantel against S. japonicum. These have included examining its unique pharmacological action on schistosomes, the characteristics in susceptibility of the different developmental stages of schistosomes to the drug, the relationship between plasma concentration of the drug and efficacy, the impact of host factors on cidal action of the drug, prevention and early treatment of schistosomal infection, as well as praziquantel-resistant schistosomiasis.

The effects of praziquantel against S. japonicum, as elucidated by the experimental studies that are reviewed in this paper, may have some reference significance for the development of new antischistosomals.

Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia.

The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70%epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery.

Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1%of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011 -2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients had been trained on self-management and all hydrocele patients had been offered free surgery.

Due to the success of the MDA and the development of health center capacity for patient care, along with benefits gained from socioeconomic improvements and other interventions against vector-borne diseases and NTDs, Cambodia was validated by the World Health Organization as achieving LF elimination as a public health problem in 2016.

Schistosomiasis in the People's Republic of China (PRC) can be traced back to antiquity. In the past 60 years, the Chinese government has made great efforts to control this persistent disease with elimination slated by 2020 through the implementation of a comprehensive control strategy. This strategy aims to reduce the role of bovines and humans as sources of infection as a pre-requisite for elimination through transmission interruption. The goal of elimination will be achievable only by the implementation of a sustainable surveillance and control system, with sensitive diagnosis a key feature so that the true disease burden is not underestimated. Currently used diagnostics lack the necessary sensitivity to accurately determine the prevalence of Schistosoma japonicum infection in areas with low infection intensities. It is of critical importance to find and treat people and to identify animals with low-level infections if the National Control Programme for China is to achieve schistosomiasis elimination.

We evaluated a real-time polymerase chain reaction (qPCR) assay using 633 human stool samples collected from five villages in Hunan, Anhui, Hubei, and Jiangxi provinces, and 182 bovine (70 cattle and 112 buffalo) stool samples obtained from four villages in Hunan, Anhui, and Jiangxi provinces in the PRC. All stool samples were subjected to the miracidium hatching test (MHT, a diagnostic procedure used in the National Schistosomiasis Control Programme) and the qPCR assay. Samples positive by MHT were subjected to either the Kato-Katz technique for humans, or the formalin-ethyl acetate sedimentation-digestion (FEA-SD) procedure for bovines, to determine infection intensities.

The qPCR assay exhibited a high level of sensitivity in the detection of S. japonicum infections. With both the human and bovine samples, a significantly higher prevalence was determined using the qPCR assay (11.06%humans, 24.73%bovines) than with the MHT (0.93%humans, 7.69%bovines). The animal contamination index (calculated using data obtained with the qPCR technique) for all positive bovines was 27 618 000 eggs per day, indicating a considerable amount of environmental egg contamination that would be underestimated using less sensitive diagnostic procedures.

The qPCR assay we have evaluated will be applicable as a future field diagnostic and surveillance tool in low-transmission zones where schistosomiasis elimination is targeted and for monitoring post-intervention areas to verify that elimination has been maintained.

As well as imposing an economic burden on affected households, the high costs related to tuberculosis (TB) can create access and adherence barriers. This highlights the particular urgency of achieving one of the End TB Strategy's targets: that no TB-affected households have to face catastrophic costs by 2020. In Indonesia, as elsewhere, there is also an emerging need to provide social protection by implementing universal health coverage (UHC). We therefore assessed the incidence of catastrophic total costs due to TB, and their determinants since the implementation of UHC.

We interviewed adult TB and multidrug-resistant TB (MDR-TB) patients in urban, suburban and rural areas of Indonesia who had been treated for at least one month or had finished treatment no more than one month earlier. Following the WHO recommendation, we assessed the incidence of catastrophic total costs due to TB. We also analyzed the sensitivity of incidence relative to several thresholds, and measured differences between poor and non-poor households in the incidence of catastrophic costs. Generalized linear mixed-model analysis was used to identify determinants of the catastrophic total costs.

We analyzed 282 TB and 64 MDR-TB patients. For TB-related services, the median (interquartile range) of total costs incurred by households was 133 USD (55-576); for MDR-TB-related services, it was 2804 USD (1008-4325). The incidence of catastrophic total costs in all TB-affected households was 36%(43%in poor households and 25%in non-poor households). For MDR-TB-affected households, the incidence was 83% (83%and 83%). In TB-affected households, the determinants of catastrophic total costs were poor households (adjusted odds ratio [aOR]=3.7, 95% confidence interval [CI]: 1.7-7.8); being a breadwinner (aOR=2.9, 95% CI: 1.3-6.6); job loss (aOR=21.2;95% CI: 8.3-53.9); and previous TB treatment (aOR=2.9; 95% CI: 1.4-6.1). In MDR-TB-affected households, having an income-earning job before diagnosis was the only determinant of catastrophic total costs (aOR=8.7; 95% CI: 1.8-41.7).

Despite the implementation of UHC, TB-affected households still risk catastrophic total costs and further impoverishment. As well as ensuring access to healthcare, a cost-mitigation policy and additional financial protection should be provided to protect the poor and relieve income losses.

The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors.

In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio^® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio^®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database.

The overall seroprevalence for DENV infection was 86.6%(240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2%(31/277) of participants, whereas there was evidence of past infection in 75.5%(209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5%in the age group of <25 years to more than 85%in age group of>45 years (P <0.001). No associations with occupation, study site, housing type, comorbidity, educational level, and marital status were observed, although the latter two were statistically significant in the univariate analysis. None of the studied factors were significantly associated with recent DENV infections in the multivariate analysis, although there was a pattern suggestive of recent outbreak in two study sites populated predominately by Chinese people. The majority of infections did not give rise to recognizable disease (either asymptomatic or nonspecific symptoms) as only 12.9%of participants (31/240) recalled having dengue in the past.

The predominantly rural community under study had a very high previous exposure to dengue. The finding of a high proportion of unreported cases possibly due to subclinical infections underscores the need for enhanced surveillance and control methods. This finding also has implications for measuring disease burden, understanding transmission dynamics, and hypothesizing effects on DENV vaccine efficacy and uptake.

The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major.

A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan.

Average costs per patients were US$ 11 (SE=0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE=7.58) (Group II: Electro-thermo-debridement [ETD]+Moist wound treatment [MWT]) and US$ 25 (SE=0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens' drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE=0.36) in Group II, 147 (SE=0.33) in Group III, and 129 (SE=0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$ 0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80%of the cases starting at a willingness-to-pay of 80 cent per wound free day.

Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure.

Cystic echinococcosis (CE) is a human and animal health problem in many endemic areas worldwide. It is considered a neglected zoonotic disease caused by the larval form (hydatid cyst) of Echinococcus spp. tapeworm. There are limited studies on echinococcosis in Pakistan.

A cross-sectional survey was conducted to find out recent knowledge, attitudes and practices on the occurrence of cystic echinococcosis in butchers and dog owners in both urban and rural areas of Rawalpindi/Islamabad regions, Pakistan. The quantitative data was collected in the form of questionnaires to investigate the knowledge and awareness of CE among community members and their routine practices that were behind the factors involved in hydatid cyst infection. The practices and infrastructure of abattoirs/butcher shops and their role in transmission of cystic echinococcosis were also evaluated in the present study.

The participants involved in the study were dog owners and people who kept animals. A total of 400people were interviewed and 289 questionnaires were received. The results showed that only 4.1% of people have heard about the disease, and 58.1%were closely associated with dogs. Sixty-three percent of dogs in study area were consuming uncooked organs (e.g. liver, lung, etc.) of slaughtered animals, while 100%of dogs at butcher shops were consuming uncooked organs. Home slaughtering was common in 20.06%. Among butchers, 32.3%had heard about zoonoses and 7.61% knew about CE. The statistical analysis showed that there was highly significant difference (P <0.05) among most of the practices that were associated with the prevalence of CE.

It was concluded from the present study that, the knowledge and awareness of CE among people of Rawalpindi/Islamabad were low. Because of dogs and poor knowledge of CE among community members and butchers, the transmission of echinococcosis is facilitated. Therefore, there is urgent need to strengthen awareness and health education among people, as well as proper practices related to the CE not only in the study area, but also in other areas of Pakistan.

Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most patients develop chronic hepatitis, with rare cases of spontaneous clearance. However, little is known about multidrug resistant viral variants in Pakistan.

This case study describes a 47-year-old male diagnosed with chronic HCV genotype 3a infection in 2003. After an initial diagnosis of viral infection, the patient remained treatment naïve for 5 years. He received two therapy cycles of interferon (IFN) plus ribavirin (RBV) in 2007 and 2010, however, he was non-responsive to the therapy. The patient then received an additional two treatment cycles of pegylated IFN α-2b plus RBV (in 2011 and 2013); he was still non-responsive. In 2016, the patient underwent sofosbuvir plus RBV combination therapy, however, the sustained virological response was still not achieved. The host genetic factor was found to be heterozygous guanine and thymine (GT) and cytosine and thymine (CT) genotypes of rs8099917 and rs12979860 polymorphism of IL28B, respectively. Phylogenetic analysis suggests that the resistant variant belong to an out-group and may require triple therapy.

This is the first case that reports on a HCV-infected individual who was a non-responder to multiple IFN therapies in Pakistan. Further studies are needed to understand multidrug-resistant HCV variants in the Pakistani population.

After publication of this article [1] it came to our attention that the name of the author Sadie Ryan was incorrectly shown. Her correct name is Sadie J. Ryan. The original article has been updated to reflect this change.