Mass drug administration for control of parasitic infections

INTRODUCTION — Empiric deworming refers to use of anthelminthic drugs to reduce the prevalence of infection due to soil-transmitted helminths in endemic areas. Such reductions in prevalence are generally temporary; mass drug administration (MDA) interrupts parasite life cycles but does not halt them completely, and the risk for reinfection is high [1,2].

Areas with high prevalence of helminth infection require a number of public health measures beyond preventive treatment, including safe drinking water, basic sanitation, and health education [3].

Issues related to population deworming are discussed here; issues related to the epidemiology, clinical manifestations, diagnosis, and treatment of individual parasitic infections are discussed separately. (See related topics.)

EFFICACY

Children — Infection due to soil-transmitted helminths has been associated with morbidity including delays in growth and cognitive development, particularly among children 2 to 12 years of age [1,4-6]. Population deworming may be effective in reducing the prevalence of infection [7]; the degree of benefit depends on patient characteristics, regional parasite species, and burden of infection.

The data on efficacy for population deworming are mixed; overall, the evidence demonstrates that children with helminth infections have diminished growth rates compared with uninfected children and that population deworming can help mitigate this issue [8-12]. The greatest benefit of deworming appears to be among young children who undergo screening prior to treatment [13].

The World Health Organization (WHO) has stated that, overall, mass treatment is not beneficial at a population level, but the WHO continues to recommend this approach since studies suggest that the children who are infected do benefit [14,15]. Targeting testing and treatment would be most beneficial, but this approach is too costly in many regions.

Studies performed in India during the 1990s suggested that deworming of malnourished children one to five years of age was associated with average weight gain of nearly one kilogram [8], and targeting worming of this age group has been advocated based on high prevalence of geohelminth infection [9]. Another study among Ugandan children one to seven years of age treated with deworming pills also concluded an association between deworming and weight gain, although the analysis did not reflect that the children were randomized in geographic clusters rather than individually [10].

Subsequently, a 2012 meta-analysis including 42 trials noted no association between deworming and child cognition, school attendance, or school performance [11]. Evidence for improvement in weight, hemoglobin level, and cognition was greatest among children screened for helminth infection prior to treatment.

The largest single trial addressing population deworming was published in 2013; it included 1 million preschool children in north India treated every six months for five years [12]. This trial noted no effect on weight gain or mortality; decline in the levels of worm infestation was observed, and compliance with treatment was high. Although the majority of children had a relatively light burden of infection, these studies were corroborated in rural China (also in light infection intensity) with no improvement on nutrition after deworming [12,16].

Repeat analysis of a previous study [17] showing favorable outcomes with deworming projects in Kenya demonstrated agreement with reductions in worm infections, but did not demonstrate a significant increase in school attendance and noted only a modest improvement in nutritional status [18,19]. The repeat analysis used the original data but documented discrepancies that reduced the statistical significance of deworming benefits [17-19].

Pregnant patients — The efficacy for population deworming among pregnant patients is also mixed [20].

A Cochrane review of six trials (including 7873 pregnant patients seen at antenatal clinics in Uganda, Nigeria, Peru, India, Sierra Leone, and Tanzania) concluded that, when used in settings with high prevalence of maternal helminthiasis, administration of a single dose of anthelminthics during the second trimester may reduce maternal anemia (risk ratio 0.85, 95% CI 0.72-1.00) and worm prevalence (trichuris: risk ratio 0.68, 95% CI 0.48-0.98; ascaris risk ratio 0.24, 95% CI 0.19-0.29) [21].

Some studies have noted an association between deworming of pregnant patients (together with iron and folic acid supplementation) and improved neonatal outcome with respect to increased birth weight and reduced infant mortality [22-25]. However, another study including more than 2000 patients in Uganda with low-intensity helminth infection noted no overall benefit of anthelminthics during pregnancy [26], and there was an increased risk of eczema among newborns [27]. A 2008 review noted data are insufficient to confirm the benefits of deworming on anemia in pregnancy [28].

One study has noted an association between helminth infection in pregnancy and malaria in offspring, suggesting that helminth infection during pregnancy may increase the burden of childhood malaria morbidity [29]. In one study in Peru, mothers infected with soil-transmitted helminths who underwent postpartum deworming were noted to have infants with improved growth [30].

It has been hypothesized that immune responses evoked by helminth infection may influence clinical susceptibility to malaria [31,32]. One randomized trial among 2436 children in Kenya noted that repeated deworming does not alter risk of clinical malaria or malaria parasitemia [33].

PARASITE TARGETS — For circumstances in which MDA is felt to be warranted, reasonable target parasite species include the following intestinal helminths:

●Ascaris lumbricoides

●Ancylostoma duodenale

●Necator americanus

●Strongyloides stercoralis

●Trichuris trichiura

Nematode (roundworm) infections include A. lumbricoides (the cause of ascariasis), A. duodenale and N. americanus (the causes of hookworm), S. stercoralis (the cause of strongyloidiasis), and T. trichiura (the cause of trichuriasis) [34]. Nematodes are transmitted via cutaneous penetration or the fecal-oral route. Population deworming in areas where nematodes are endemic may be warranted among children who have undergone screening, even though reinfection rates are high [35]. (See "Ascariasis" and "Hookworm infection" and "Strongyloidiasis".)

Empiric deworming is not an accepted prevention method for most regions with endemic cestode (tapeworm) infections (such as taeniasis, diphyllobothriasis, and hymenolepiasis) [36]. These infections are transmitted via contaminated food; prevention measures generally consist of controlling animal vectors, sanitation, and hygiene [36,37]. Population deworming may be useful for short-term control of transmission in some circumstances [38]. (See "Tapeworm infections".)

Issues related to MDA for control of schistosomiasis are discussed separately. (See "Schistosomiasis: Treatment and prevention", section on 'Control and prevention'.)

Issues related to mass treatment for filariasis are discussed separately (see "Onchocerciasis", section on 'Mass treatment' and "Lymphatic filariasis: Treatment and prevention", section on 'Mass treatment').

CLINICAL APPROACH

Patient groups to target — The greatest benefit of deworming has been among young children who undergo screening prior to treatment.

In general, pregnant women should undergo diagnostic evaluation with stool examination for ova and parasites, and treatment should be administered for pathogens identified (in lieu of empiric therapy) [39]. Empiric treatment may be reasonable for HIV-infected pregnant women [40]; further study is needed.

Evidence is weakest for routine deworming among nonpregnant adults in regions with endemic geohelminths.

Logistics of administration — The optimal approach to MDA is uncertain; modalities include community-based or school-based programs. A community-based approach may be more effective in reducing parasite prevalence than school-based administration [41,42], but school-based administration is logistically easier, less expensive, and has been shown to have some efficacy in reducing parasite prevalence [43].

In a cluster-randomized trial including 150,000 Kenyan households, albendazole was administered via annual school-based treatment targeting 2 to 14 year olds or via community-wide treatment targeting all ages (administered annually or biannually) [41]. After 24 months, the reduction in hookworm prevalence was greater in areas of community-wide treatment than in areas of school-based treatment (risk ratio 0.59 [95% CI 0.42-0·83] for annual community-wide treatment; risk ratio 0.46 [95% CI 0.33-0·63] for biannual community-wide treatment). No adverse events related to albendazole were reported.

Deworming regimens — Anthelminthic agents should be selected for activity against regional helminth species and to minimize adverse effects.

In the absence of detailed information regarding the predominant regional helminth species, a deworming regimen consisting of albendazole (400 mg orally once on empty stomach) and ivermectin (200 mcg/kg orally once) may be administered. Issues related to pregnancy are discussed below. (See 'Pregnancy considerations' below.)

Ivermectin should not be used empirically among populations at risk of loaiasis in Africa. Albendazole-ivermectin has efficacy for reduction of infection due to A. lumbricoides, Enterobius vermicularis, hookworm, S. stercoralis, and T. trichiura. Drug administration should be repeated at 6- to 12-month intervals with assessment of egg-reduction rates [44].

When possible, deworming regimens should be tailored to the predominant regional helminth species, as follows:

●Ascariasis and/or hookworm - In regions known to have a high burden of ascariasis and/or hookworm, treatment consists of albendazole (children or nonpregnant adults: 400 mg orally once on empty stomach) or mebendazole (children or nonpregnant adults: 500 mg orally once). Ascariasis cure rates with these drugs are 96 to 100 percent; hookworm cure rates are 72 to 80 percent [45,46].

For pregnant patients, a reasonable alternative regimen is pyrantel pamoate (11 mg/kg orally once for ascariasis; 11 mg/kg once daily for three days for hookworm). Issues related to use of albendazole and mebendazole in pregnancy are discussed below. (See 'Pregnancy considerations' below.)

Retreatment at 6- or 12-month intervals is appropriate [47]. Retreatment should be based on prevalence of helminthic infection in the population. Populations in high-risk areas (>50 percent prevalence) should receive retreatment at 6 months, populations in moderate-risk areas (between 20 and 50 percent prevalence) every 12 months, and retreatment of populations in areas with less than 20 percent prevalence is usually not indicated [47].

●Strongyloidiasis - In regions known to have a high burden of strongyloidiasis (tropical and subtropical regions), treatment consists of ivermectin (adults and children >15 kg: 200 mcg/kg orally once; children <2 years or <15 kg: contraindicated); the cure rate is 97 percent [48]. Albendazole (adults: 400 mg orally on empty stomach twice daily for 7 days; children 400 mg orally on empty stomach twice daily for 7 days) is an alternative choice; the cure rate is 63 percent [48].

For pregnant patients, mass treatment should be deferred until after delivery, and breast feeding should be suspended during treatment.

Issues related to ivermectin contraindications are discussed below. (See 'Contraindications to ivermectin' below.)

Deworming for strongyloidiasis is important when considering complications with hyperinfection and disseminated strongyloidiasis. Mass administration of ivermectin in other control programs such as those targeting scabies have also resulted in a decrease prevalence of strongyloidiasis in target populations [49,50].  

●Trichuriasis - In regions known to have a high burden of trichuriasis, treatment consists of a combination of albendazole and ivermectin [46,51,52]. Retreatment at 6- or 12-month intervals is appropriate [47].

Issues related to pregnancy and ivermectin contraindications are discussed below. (See 'Pregnancy considerations' below and 'Contraindications to ivermectin' below.)

One study including 450 children with trichuriasis noted that treatment with oxantel pamoate (20 mg/kg single dose) and albendazole (400 mg single dose) resulted in higher cure rates than albendazole or mebendazole alone (31 and 42 percent, respectively); the former regimen is reasonable in regions where available [53].

Pregnancy considerations — For pregnant patients in areas where the prevalence of hookworm and/or trichuriasis is ≥20 percent and the prevalence of anemia in pregnancy is ≥40 percent, we are in agreement with the World Health Organization, which favors administration of anthelminthic treatment after the first trimester [54]. In such cases, treatment consists of albendazole (400 mg single dose) or mebendazole (500 mg single dose).

Breast feeding should be suspended during the use of albendazole or mebendazole due to high drug levels in breast milk.

Ivermectin should not be administered to pregnant or lactating women.

Contraindications to ivermectin — Ivermectin should not be administered to pregnant women, children <2 years or <15 kg, patients with liver disease, or patients in western Africa who are at risk for Loa loa infection [55,56]. Breast feeding should be suspended during the use of ivermectin due to high drug levels in breast milk.

Other issues related to anthelminthic drugs, including adverse effects, are discussed separately. (See "Anthelminthic therapies".)

ADHERENCE — Important barriers for gaps in implementation of MDA include lack of adequate drug delivery and insufficient health education. In one study of MDA in Uganda, factors associated with reduced likelihood of MDA participation included lower socioeconomic standing, membership in a religious or underrepresented ethnic group, longer residence in a location, and lack of a household latrine [57]. Other factors included relatively high intensity of S. mansoni infection and high hookworm prevalence.

SUMMARY

●Population deworming refers to empiric use of anthelminthic drugs to reduce the prevalence of infection due to soil-transmitted helminths in endemic areas. Such reductions in prevalence are generally temporary; mass drug administration interrupts parasite life cycles but does not halt them completely, and the risk for reinfection is high. (See 'Introduction' above.)

●The greatest benefit of deworming appears to be among young children who undergo screening prior to treatment. In general, diagnostic evaluation with stool examination for ova and parasites should be performed for such patients, with administration of treatment for pathogens identified. (See 'Efficacy' above.)

●Reasonable target intestinal helminth species for deworming include Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, and Trichuris trichiura. (See 'Parasite targets' above.)

●Anthelminthic agents should be selected for activity against regional helminth species and to minimize adverse effects. In the absence of detailed information regarding the predominant regional helminth species, a deworming regimen consisting of albendazole and ivermectin may be administered. Drug administration should be repeated at 6- to 12-month intervals with monitoring for decreasing prevalence of infection. Ivermectin should not be used empirically among populations at risk of loaiasis in Africa. (See 'Clinical approach' above.)

●For pregnant patients in areas where the prevalence of hookworm and/or trichuriasis is ≥20 percent and the prevalence of anemia in pregnancy is ≥40 percent, we suggest administration of anthelminthic treatment after the first trimester (Grade 2C); regimens include albendazole or mebendazole. (See 'Pregnancy considerations' above.)

●Ivermectin should not be administered to pregnant women, children <2 years of age or <15 kg, patients with liver disease, or patients in western Africa who are at risk for Loa loa infection. (See 'Contraindications to ivermectin' above.)