Mass Treatment Strategies Research Articles

Quantifying ivermectin's optimal strategy impacts on malaria transmission: a dual-structured mathematical model

Ivermectin (IVM), used alongside mass treatment strategies, has been suggested as a potential tool for reducing malaria transmission. The effectiveness of IVM in shortening vector lifespan depends on the time elapsed between the administration of IVM to the host and the blood meal taken by the vector. This effectiveness is measured by the median effective dose ( ED 50 ), the IVM concentration required to kill 50% of mosquitoes after a specific host exposure period. We use a mathematical model structured by human and vector exposure times to IVM and the model's well-posedness is established through semigroups theory. We calculate the basic reproduction number, linking it to epidemiological dynamics, and show steady states bifurcate at R 0 = 1 , governed by a constant C bif . We identify the optimal human exposure to IVM and intervention interval to reduce prevalence by 10% to 20%. This depends on the IVM formulation ( ED 50 ) and the target number of campaigns in the host population.

In vivo analysis of trypanocidal drug resistance in sahelian goats infected by Trypanosoma vivax strains collected in northern Togo

Trypanosoma (T.) vivax is one of the animal trypanosomes species causing calf mortality and economic losses in Togo. Despite its importance as the most widely distributed trypanosome species, T. vivax has received little attention because it is difficult to cultivate most field isolates in rodents. No molecular diagnostic tools for the identification of drug-resistant in T. vivax are currently available. Herein, four field isolates of T. vivax from Togo were cryopreserved and assessed for susceptibility to diminazene aceturate (DA) and isometamidium chloride (ISM) in goats. For field isolate preparation, 1 ml of blood from an infected goat was diluted in 111 µl of phosphate-buffered-saline and stored in liquid nitrogen. The in vivo experiment drug test was performed using twenty Sahelian goats with six-month of age and weighing 14.5 ± 1.6 kg. These experimental goats were purchased from a tsetse free-area Dori, a Sahelian region of Burkina Faso. The cryopreserved T. vivax isolates with unknowns, DA, and ISM sensitivity was inoculated to five goats and one goat was used as control. Each animal was inoculated by intravenously route 1 × 105 trypanosomes from the donor goat. Relapses were earlier in the first phase of treatment (14.85 ± 1.08 days) compared with the second phase (20 ± 3.39 days). The overall mean PCV of the control group decreased from 32% to 17% at day-60 (P-value < 0.001). Three isolates were phenotypically resistant to 0.5 mg per kg body weight (BW) ISM and one for 3.5 mg per kg BW of DA. There were no relapses with the 7 mg per kg BW dose DA. This study shows the resistance of T. vivax to two main trypanocidal drugs in different villages of Mango. The results suggest the extension of surveillance strategies to remote villages in Togo and will guide the veterinarian or herder in choosing a mass treatment strategy. Further studies will be needed to better understand the molecular basis of the observed resistance.

What are effective mass treatment strategies for prevention of Shistosomiasis mansoni infections?

Shastry, Disha L. MD; Monichan, Ruby MD; Preciado, Martin MD; Satchell, Leneika DOAuthor Information

Bulinus senegalensis and Bulinus umbilicatus Snail Infestations by the Schistosoma haematobium Group in Niakhar, Senegal

Thorough knowledge of the dynamics of Bulinus spp. infestation could help to control the spread of schistosomiasis. This study describes the spatio-temporal dynamics of B. senegalensis and B. umbilicatus infestation by the Schistosoma haematobium group of blood flukes in Niakhar, Senegal. Molecular identification of the S. haematobium group was performed by real-time PCR, targeting the Dra 1 gene in 810 samples of Bulinus spp. collected during the schistosomiasis transmission season in 2013. In addition to Dra 1 PCR, a rapid diagnostic-PCR was performed on a sub-group of 43 snails to discriminate S. haematobium, S. bovis, and S. mattheei. Out of 810 snails, 236 (29.1%) were positive for Dra 1 based on the PCR, including 96.2% and 3.8% of B. senegalensis and B. umbilicatus, respectively. Among the sub-group, 16 samples were confirmed to be S. haematobium while one was identified as a mixture of S. haematobium and S. bovis. Snails infestations were detected in all villages sampled and infestation rates ranged from 15.38% to 42.11%. The prevalence of infestation was higher in the north (33.47%) compared to the south (25.74%). Snail populations infestations appear early in the rainy season, with a peak in the middle of the season, and then a decline towards the end of the rainy season. Molecular techniques showed, for the first time, the presence of S. bovis in the Bulinus spp. population of Niakhar. The heterogeneity of snail infestations at the village level must be taken into account in mass treatment strategies. Further studies should help to improve the characterizations of the schistosome population.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial

SummaryBackgroundSchool-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection.MethodsIn this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2–14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772.FindingsAfter 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9–23·2) to 13·8% (10·5–17·0) in the annual school-based treatment group, 17·9% (13·7–22·1) to 8·0% (6·0–10·1) in the annual community-wide treatment group, and 20·6% (15·8–25·5) to 6·2% (4·9–7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42–0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33–0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported.InterpretationCommunity-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects.FundingBill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

The potential impact of adding ivermectin to a mass treatment intervention to reduce malaria transmission: a modelling study.

Ivermectin (IVM), used alongside mass treatment strategies with an artemisinin combination therapy, has been suggested as a possible tool for reducing malaria transmission. Mosquitoes ingesting a bloodmeal containing IVM have increased mortality, reducing the probability that the parasite completes sporogony. Human pharmacokinetic data and mortality data for mosquitoes taking bloodmeals containing IVM are used to quantify the mosquitocidal effect of IVM. These are incorporated into a transmission model to estimate the impact of IVM in combination with mass treatment strategies with artemether-lumefantrine on transmission metrics. Adding IVM increases the reductions in parasite prevalence achieved and delays the reemergence of parasites compared to mass treatment alone. This transmission effect is obtained through its effect on vector mortality. IVM effectiveness depends on coverage with the highest impact achieved if given to the whole population rather than only those with existing detectable parasites. Our results suggest that including IVM in a mass treatment strategy can reduce the time taken to interrupt transmission as well as help to achieve transmission interruption in transmission settings in which mass treatment strategies alone would be insufficient. Including IVM in mass treatment strategies could be a useful adjunct to reduce and interrupt malaria transmission.

Mass primaquine treatment to eliminate vivax malaria: lessons from the past.

Recent successes in malaria control have put malaria eradication back on the public health agenda. A significant obstacle to malaria elimination in Asia is the large burden of Plasmodium vivax, which is more difficult to eliminate than Plasmodium falciparum. Persistent P. vivax liver stages can be eliminated only by radical treatment with a ≥ seven-day course of an 8-aminoquinoline, with the attendant risk of acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Primaquine is the only generally available 8-aminoquinoline. Testing for G6PD deficiency is not widely available, and so whilst it is widely recommended, primaquine is often not prescribed. In the past, some countries aiming for vivax malaria eradication deployed mass treatments with primaquine on a massive scale, without G6PD testing. In Azerbaijan, Tajikistan (formerly USSR), North Afghanistan and DPR Korea 8,270,185 people received either a 14-day “standard” or a 17-day “interrupted” primaquine treatment to control post-eradication malaria epidemics. These mass primaquine preventive treatment campaigns were conducted by dedicated teams who administered the drugs under supervision and then monitored the population for adverse events. Despite estimated G6PD prevalences up to 38.7%, the reported frequency of severe adverse events related to primaquine was very low. This experience shows that with careful planning and implementation of mass treatment strategies using primaquine and adequate medical support to manage haemolytic toxicity, it is possible to achieve high population coverage, substantially reduce malaria transmission, and manage the risk of severe acute haemolytic anaemia in communities with a relatively high prevalence of G6PD deficiency safely.

The Easiest Children to Reach Are Most Likely to Be Infected with Ocular Chlamydia trachomatis in Trachoma Endemic Areas of Niger

BackgroundControl programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected, we compare the order of presentation for examination of children 0–5 years, and the presence of ocular Chlamydia by PCR in 4 villages in Niger where trachoma is endemic.MethodsWe conducted a cluster-randomized, controlled trial where 48 randomly selected villages in Niger are divided into 4 study arms of different mass treatment strategies. In a substudy of the main trial, we randomly selected 1 village from each of the 4 study arms (4 total villages) and we evaluated the odds of ocular Chlamydia versus the rank order of presentation for examination and laboratory assessment before treatment was offered.FindingsWe found the odds of harboring ocular Chlamydia dropped by more than 70% from the first child examined to the last child examined (OR 0.27, 95% CI 0.13–0.59, P = 0.001) in the 4 randomly selected villages. We found the odds of active trachoma dropped by 80% from the first child examined to the last child examined (OR 0.20, 95% CI 0.10–0.4, P<0.0001) in the 48 villages in the main trial.InterpretationThis study demonstrates that even if the WHO recommended 80% treatment coverage is not reached in certain settings, children 0–5 years with the greatest probability of ocular Chlamydia have higher odds of receiving attention because they are the first to present. These results suggest there may be diminishing returns when using scarce resources to track down the last few children in a mass treatment program.Trial RegistrationClinicalTrials.gov NCT00792922

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden

BackgroundPast experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management.MethodsMSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT.ResultsMSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further.ConclusionsIn all the transmission settings considered, achieving a minimal level of ITN coverage is a “best buy”. At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.

The Potential Contribution of Mass Treatment to the Control of Plasmodium falciparum Malaria

Mass treatment as a means to reducing P. falciparum malaria transmission was used during the first global malaria eradication campaign and is increasingly being considered for current control programmes. We used a previously developed mathematical transmission model to explore both the short and long-term impact of possible mass treatment strategies in different scenarios of endemic transmission. Mass treatment is predicted to provide a longer-term benefit in areas with lower malaria transmission, with reduced transmission levels for at least 2 years after mass treatment is ended in a scenario where the baseline slide-prevalence is 5%, compared to less than one year in a scenario with baseline slide-prevalence at 50%. However, repeated annual mass treatment at 80% coverage could achieve around 25% reduction in infectious bites in moderate-to-high transmission settings if sustained. Using vector control could reduce transmission to levels at which mass treatment has a longer-term impact. In a limited number of settings (which have isolated transmission in small populations of 1000–10,000 with low-to-medium levels of baseline transmission) we find that five closely spaced rounds of mass treatment combined with vector control could make at least temporary elimination a feasible goal. We also estimate the effects of using gametocytocidal treatments such as primaquine and of restricting treatment to parasite-positive individuals. In conclusion, mass treatment needs to be repeated or combined with other interventions for long-term impact in many endemic settings. The benefits of mass treatment need to be carefully weighed against the risks of increasing drug selection pressure.

The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

BackgroundThe natural history of ocular Chlamydia trachomatis infections in endemic communities has not been well characterised and is an important determinant of the effectiveness of different mass treatment strategies to prevent blindness due to trachoma.Methodology/Principal FindingsA multistate hidden Markov model was fitted to data on infection and active disease from 256 untreated villagers in The Gambia who were examined every 2 weeks over a 6-month period. Parameters defining the natural history of trachoma were estimated, and associations between these parameters, demographic and baseline immune measurements examined. The median incubation period following infection was estimated at 17 days (95% confidence interval: 11–28). Disease persisted for longer than infection (median 21 (15–32) weeks) versus 17 (12–24) weeks), with an estimated median duration of post-infection inflammation of 5 (3–8) weeks. The duration of active disease showed a significant decline with age even after accounting for lower rates of re-infection and disease at older ages (p = 0.004). Measurements of levels of baseline IgA to epitopes in the major outer membrane protein of Chlamydia trachomatis were not significantly correlated with protection or more rapid clearance of infection.ConclusionsThe average duration of infection with Chlamydia trachomatis especially at younger ages is long. This contributes to the persistence and gradual return of trachoma after community-wide treatment with antibiotics.

Mass Treatment and the Effect on the Load ofChlamydia trachomatisInfection in a Trachoma-Hyperendemic Community

Trachoma remains a leading cause of blindness. Determining the most effective antibiotic treatment strategy is essential for the success of country-based trachoma control programs. Baseline and 2-month follow-up examinations were performed in a trachoma-hyperendemic village. All residents were offered azithromycin for trachoma after baseline was determined. Infection with Chlamydia trachomatis and chlamydial load were determined by PCR. Clinical trachoma status was evaluated. A high chlamydial load was defined as a higher than median chlamydial load among those with infection. Risk factors were examined in multiple logistic regression models. Associations are presented as odds ratios and 95% confidence intervals. At baseline, 57% of participants were infected with C. trachomatis. Although clinical trachoma correlated with infection, 23% of participants with high chlamydial loads showed no clinical signs. Adults represented only 10% of the population with high loads. Treatment significantly decreased the proportion positive in the community and the load in the community. However, 27% of individuals with high loads at baseline who received treatment also were infected at 2 months. Of those, 93% with high loads at 2 months were aged < or =10 years. Although most of the chlamydial load in this community resided in children, 10% of the high load resided in adults, most of whom did not have follicular trachoma and in whom the infection would be missed under treatment strategies that focus on clinical disease or children. These data support a mass treatment strategy for hyperendemic communities, at least as a first approach. In addition, treatment of children age < or =2 years should be reexamined, as >30% with high loads at baseline remained infected at 2 months, despite monitored treatment according to weight.

One in the eye for river blindness

This Journal Club article also appears in Trends in ParasitologyChemotherapy is the principal intervention in the control of filariasis. For Onchocerca volvulus, the species responsible for ‘river blindness’, the current approach is to treat with ivermectin (Mectizan), a drug highly effective at clearing the juvenile microfilarial stage of the parasite, which lives in the skin awaiting transmission by the blackfly vector. Unfortunately, Mectizan has no effect on the survival of adult worms, which can live for a decade or more in subcutaneous nodules, giving birth to millions of microfilariae. Consequently, treatment has to be repeated on an annual basis for several years and cover sufficient numbers of people to have any hope of interrupting transmission. For years, scientists have been searching for that elusive drug that can kill or permanently sterilize the long-lived adult nematodes, but with little success. Recently, a new target for anti-filarial chemotherapy has emerged from the revelation that intracellular Wolbachia bacteria have evolved an obligate symbiosis with their nematode hosts. Treatment of filarial nematodes with the antibiotics tetracycline or rifampicin leads to the depletion of Wolbachia, and results in long-term sterility and inhibition of worm development and viability. In the few years since this discovery, the first clinical trial to test the effect of antibiotics on the depletion of Wolbachia in human onchocerciasis has been completed in Ghana 1xDepletion of Wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Hoerauf, A. et al. Lancet. 2001; 357: 1415–1416Abstract | Full Text | Full Text PDF | PubMed | Scopus (167)See all

Urethral Trichomonas vaginalis infection and HIV-1 transmission

The authors' previous study of 504 male workers in Mombasa, Kenya, provides further documentation of an association between urethral infection and increased shedding of HIV in semen. In this study, Trichomonas vaginalis was isolated by culture in 30 men (6%) and was the most commonly isolated urethral pathogen. Men with Trichomonas vaginalis were significantly older than those with Neisseria gonorrhoeae, suggesting infection may be of long duration. 83% of men with unmixed infections were asymptomatic. Since guidelines for syndromic management of urethral discharge do not include Trichomonas vaginalis, even symptomatic men with this condition who seek treatment are unlikely to be diagnosed and properly treated. More research is needed to confirm whether Trichomonas vaginalis (especially long-standing, low-grade infection) enhances male to female HIV transmission. Since an effective, single-dose, low-cost treatment for Trichomonas vaginalis is available worldwide, mass treatment strategies for this sexually transmitted disease could play an important part in HIV prevention in developing countries.

Effect of age on the efficacy of blood pressure treatment strategies.

To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort. We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45-54 years of age, only 30-40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure greater than or equal to 160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially; in the older age group (greater than or equal to 75 years), 65-70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflections on the U.S. preventive services task force recommendations for screening for hypertension and hypercholesterolemia

The U.S. Preventive Services Task Force recommendations for screening for hypertension and high blood cholesterol are generally consistent with preexisting national guidelines promulgated by the Joint National Committee for Detection, Evaluation, and Treatment of High Blood Pressure and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults. While a welcome addition to the armamentarium of the clinician, the Task Force recommendations represent only a partial solution to our current epidemic of blood-pressure- and cholesterol-related cardiovascular disease. A meaningful reduction in society's burden of cardiovascular disease can be achieved only by complementing the Task Force recommendations with community-based mass treatment strategies aimed at shifting the distribution of blood pressure and cholesterol toward a biologically more normal pattern.