Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework.

As national programmes respond to the new opportunities presented for scaling up preventive chemotherapy programmes for the coadministration of drugs to target lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma, possible synergies between existing disease-specific policies and protocols need to be examined. In this report we compare present policies for mapping, monitoring, and surveillance for these diseases, drawing attention to both the challenges and opportunities for integration. Although full integration of all elements of mapping, monitoring, and surveillance strategies might not be feasible for the diseases targeted through the preventive chemotherapy approach, there are opportunities for integration, and we present examples of integrated strategies. Finally, if advantage is to be taken of scaled up interventions to address neglected tropical diseases, efforts to develop rapid, inexpensive, and easy-to-use methods, whether disease-specific or integrated, should be increased. We present a framework for development of an integrated monitoring and evaluation system that combines both integrated and disease-specific strategies.

Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.

Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-1(19) from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice. In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-1(19)-based vaccines.

Significant decline in lymphatic filariasis associated with nationwide scale-up of insecticide-treated nets in Zambia.

Lymphatic filariasis (LF) is a mosquito-borne disease, broadly endemic in Zambia, and is targeted for elimination by mass drug administration (MDA) of albendazole and diethylcarbamazine citrate (DEC) to at-risk populations. Anopheline mosquitoes are primary vectors of LF in Africa, and it is possible that the significant scale-up of malaria vector control over the past decade may have also impacted LF transmission, and contributed to a decrease in prevalence in Zambia. We therefore aimed to examine the putative association between decreasing LF prevalence and increasing coverage of insecticide-treated mosquito nets (ITNs) for malaria vector control, by comparing LF mapping data collected between 2003-2005 and 2009-2011 to LF sentinel site prevalence data collected between 2012 and 2014, before any anti-LF MDA was started. The coverage of ITNs for malaria was quantified and compared for each site in relation to the dynamics of LF. We found a significant decrease in LF prevalence from the years 2003-2005 (11.5% CI95 6.6; 16.4) to 2012-2014 (0.6% CI95 0.03; 1.1); at the same time, there was a significant scale-up of ITNs across the country from 0.2% (CI95 0.0; 0.3) to 76.1% (CI95 71.4; 80.7) respectively. The creation and comparison of two linear models demonstrated that the geographical and temporal variation in ITN coverage was a better predictor of LF prevalence than year alone. Whilst a causal relationship between LF prevalence and ITN coverage cannot be proved, we propose that the scale-up of ITNs has helped to control Anopheles mosquito populations, which have in turn impacted on LF transmission significantly before the scale-up of MDA. This putative synergy with vector control has helped to put Zambia on track to meet national and global goals of LF elimination by 2020.

Modelling strategies to break transmission of lymphatic filariasis--aggregation, adherence and vector competence greatly alter elimination.

BACKGROUND: With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. METHODS: We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. RESULTS: In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. CONCLUSION: Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination.

Transmission dynamics of Wuchereria bancrofti in East Sepik Province, Papua New Guinea.

Bancroftian filariasis is endemic in many areas of Papua New Guinea. This study describes the entomologic indices of transmission near Dreikikir in East Sepik Province, Papua New Guinea. A total of 1,735 culicine mosquitoes, including Culex and Mansonia species, were dissected, but none were infected with filarial larvae. In contrast, Anopheles punctulatus and An. koliensis were found to be potential vectors: 7.3% of Anopheles were infected and the mean number of first- to third-stage larvae per infected mosquito was 2.7. Transmission indices varied significantly in five villages located within a 50-km radius of each other. Annual biting rates ranged from 4,789 to 48,020 bites/person/year; annual infective biting rates from 15 to 836/person/year; and annual transmission potential from 31 to 2,340 third-stage larvae/person/year. Monthly transmission potential and monthly infective biting rate varied significantly in each village, with the highest indices of transmission observed in villages nearest sites where puddles formed in river beds during the dry season. These data indicate that there is small area variation in the intensity and temporal pattern of filariasis transmission and that culicine mosquitoes are not important vectors of W. bancrofti in this area.

Random distribution of mixed species malaria infections in Papua New Guinea.

Plasmodium falciparum (Pf), P. vivax (Pv), P. malariae (Pm), and P. ovale (Po) infections are endemic in coastal areas of Papua New Guinea. Here 2,162 individuals living near Dreikikir, East Sepik Province, have been analyzed for complexity of malaria infection by blood smear and polymerase chain reaction (PCR) diagnoses. According to blood smear, the overall prevalence of Plasmodium infection was 0.320. Most individuals (0.283) were infected with a single species only. The prevalence of mixed species infections was low (0.037). Further analysis of a 173-sample subset by nested PCR of small subunit ribosomal DNA resulted in an overall 3.0-fold increase in prevalence of infection, with a 17.5-fold increase in the frequency of mixed species infections. Among mixed species infections detected by PCR, the frequency of double species was 0.364, and that of triple species was 0.237. Nine individuals (0.052) were infected with all 4 species. To determine if infection status (uninfected, single, and multiple infections) deviates from an independent random distribution (null hypothesis), observed versus expected frequencies of all combinations of Plasmodium species infections, or assemblages (Pf-, Pv-, Pm-, Po-, to Pf+, Pv+, Pm+, Po+), were compared using a multiple-kind lottery model. All 4 species were randomly distributed whether diagnosed by blood smear or PCR in the overall population and when divided into age group categories. These findings suggest that mixed species malaria infections are common, and that Plasmodium species appear to establish infection independent of one another.

Application of a polymerase chain reaction-ELISA to detect Wuchereria bancrofti in pools of wild-caught Anopheles punctulatus in a filariasis control area in Papua New Guinea.

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancrofti by its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P = 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P = 0.84), but the overall infection rate of light-trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P = 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low.

Isolation of Japanese encephalitis virus from mosquitoes (Diptera: Culicidae) collected in the Western Province of Papua New Guinea, 1997-1998.

After Japanese encephalitis (JE) virus emerged in the Torres Strait in Australia in 1995, investigations were initiated into the origin of the incursion. New Guinea was considered the most likely source, given its proximity to islands of the Torres Strait. Almost 400,000 adult mosquitoes were processed for virus isolation from 26 locations in the Western Province of Papua New Guinea (PNG) between February 1996 and February 1998, yielding three isolates of JE virus. Two isolates of Murray Valley encephalitis, 17 isolates of Sindbis, and 1 each of Sepik and Ross River viruses were also obtained. Nucleic acid sequences of the PNG JE isolates were determined in the prM region, and in a region overlapping a part of the fifth nonstructural protein and the 3' untranslated region. The PNG isolates belonged to genotype II, and shared > 99.2% identity with isolates from humans and mosquitoes from the Torres Strait, suggesting that PNG is the source of incursions of JE virus into Australia.

The late biting habit of parous Anopheles mosquitoes and pre-bedtime exposure of humans to infective female mosquitoes.

Using the all-night landing catch method (18:00-06:00) we showed, for Anopheles gambiae in Sierra Leone and A. punctulatus in Papua New Guinea, that parous females have a tendency to bite later than nulliparous ones. The biting habit of sporozoite-infected A. punctulatus was also investigated. The sporozoite rates for Plasmodium falciparum and P. vivax were 1.8 and 1.4% respectively, but only one (1.3%) of 76 females infected with P. falciparum was caught between 18:00 and 21:00. A significantly higher proportion (11.6%) of mosquitoes infected with P. vivax was caught in the same period. The late biting habit of mosquitoes infected with P. falciparum is discussed in relation to the differential biting habits of parous and nulliparous females. We conclude with a hypothesis that, in areas where Anopheles mosquitoes have a late-biting cycle and low parous rate, exposure to mosquitoes infected with P. falciparum during the pre-bedtime period (18:00-22:00) is very low. This hypothesis could explain why insecticide-treated bed nets protect children better in areas of seasonal transmission, where nulliparous females tend to predominate, than in areas of perennial transmission, where parous females are usually more numerous. The same hypothesis is compatible with the finding in Papua New Guinea that insecticide-impregnated bed nets are more protective against P. falciparum than against P. vivax malaria.

The epidemiology of malaria in southern Sierra Leone.

The epidemiology of malaria was investigated in a high rainfall, forested area of southern Sierra Leone. The prevalence rates of P. falciparum, P. malariae and P. ovale in 0-7 year old children, during two surveys conducted over a 12-month period, averaged 61%, 12% and 1% respectively. Groups of febrile children had higher prevalence rates than afebrile groups. Overall, gametocyte rates were approximately one fifth of the trophozoite rates. Malaria accounted for 27% of deaths, as did malnutrition, although no malaria associated deaths occurred in 0-12 month olds. Spleen rates were similar to P. falciparum prevalence rates, and the size did not appear to be related to parasite load at the time of the surveys. Packed cell volumes had normal distributions, with a lower mode after the peak prevalence period. Chloroquine usage increased during the post-rains period compared to the pre-rains period.

The ecology and behaviour of the forest form of Anopheles gambiae s.s.

Studies on the ecology of Anopheles gambiae s.s. and the transmission of malaria were undertaken in a high rainfall forested area in southern Sierra Leone. Anopheles gambiae s.s., identified by chromosomal techniques as the Forest form, was the only malaria vector in the study village. Surprisingly, rice fields or swamps were not favoured breeding places for this species; breeding mainly occurred in temporary pools. The mean annual sporozoite rate of An. gambiae s.s. determined by ELISA was 3.9%. Pyrethrum spray, human bait, and exit trap collections, as well as identification of mosquito blood-meals using the ELISA method, showed that the forest chromosomal form of An. gambiae s.s. was highly anthropophagic and exophilic.

Can mosquitoes transmit AIDS?

Surveys to determine knowledge regarding AIDS have shown in many countries, including Papua New Guinea, that a large proportion of the literate population still mistakenly believe that mosquitoes can transmit the AIDS virus from one person to another. In this paper we review the theoretical mechanisms which would allow blood-sucking insects such as mosquitoes to transmit virus and discuss the evidence against transmission of HIV by mosquitoes. AIDS is a sexually transmitted disease with no scientific evidence for arthropod transmission.

PIP: Surveys in many countries, including Papua New Guinea, show that a large proportion of the literate population still believe the fallacy that mosquitoes can transmit the AIDS virus from one person to another. Since AIDS was first recognized, many have reported on the possibility of mosquito involvement in the transmission of the virus. In 1988, almost half of 6625 men and women interviewed in Zaire and nearly half of 4189 teacher-trainees interviewed in Zimbabwe believed in the transmission of AIDS by mosquitoes. A recent survey involving 1500 high school students from 14 schools in 4 different provinces in Papua New Guinea revealed that 34% of them considered mosquitoes to be carriers of HIV. Although mosquitoes are carriers of yellow fever, dengue fever, and Japanese encephalitis, there is no evidence that mosquitoes can transmit HIV. Studies with HIV have shown clearly that the virus disappears in the mosquito after about 1-2 days, the time required for the mosquito to digest the blood-meal. Since the virus does not survive to reproduce and invade the salivary glands, biological transmission of HIV is not possible. It has been calculated that, for mechanical transmission, an AIDS-free individual would have to be bitten by 10 million mosquitoes that had been feeding on an HIV carrier to receive a single unit of HIV from contaminated mosquito mouthparts. In short, there is still no evidence of arthropod transmission of the HIV virus.

Control of lymphatic filariasis in a hunter-gatherer group in Madang Province.

Diethylcarbamazine (DEC) has been successfully administered to millions of people in established villages and towns, but little or no information exists on the use of this drug to control lymphatic filariasis in isolated seminomadic groups. We have studied the impact of biannual single-dose mass treatment to control filariasis in the Hagahai, an isolated hunter-gatherer, shifting horticulturist group in the fringe highlands of Papua New Guinea. Despite low treatment coverage, 6 mass treatment rounds significantly reduced the overall prevalence of infection with Wuchereria bancrofti, by antigen detection assay, from 55% before treatment to 34% after treatment. Obstructive filarial disease in the form of elephantiasis or hydrocele was not observed among the indigenous population. Anopheles species accounted for 91% of human-biting mosquitoes collected in the area. A total of 1126 mosquitoes were caught and dissected individually but none was infected with third-stage larvae (L3). Our findings support the phenomenon of facilitation, which predicts that Anopheles-transmitted lymphatic filariasis can be interrupted by mass chemotherapy alone in areas of low vector density and low transmission intensity as observed in the Hagahai.

The epidemiology and control of lymphatic filariasis on Lihir Island, New Ireland Province.

Clinical, parasitological and entomological surveys performed in 9 villages on Lihir Island, Papua New Guinea, before mass treatment with diethylcarbamazine (DEC), showed that lymphatic filariasis, caused by nocturnally periodic Wuchereria bancrofti, was endemic in 8 of them. Blood samples from 593 people revealed an overall microfilarial carrier rate of 24%. Amongst endemic villages, microfilarial carrier rates ranged from 5% to 43% and there was no significant difference in parasite prevalence between males and females. Obstructive filarial disease, defined as lymphoedema of the limbs or hydrocele, was observed in only 2% of 262 males examined. None of the 265 females examined had clinical symptoms. Entomological surveys yielded a total of 4095 mosquitoes including 3,692 anophelines and 241 culicines but only Anopheles farauti was found to harbour infective larvae of W. bancrofti. Pretreatment infection and infective rates of An. farauti were 7% and 1% respectively and up to 12 infective larvae were found in a single specimen. The microfilarial carrier rate in a cohort of people who received two DEC treatments dropped from 59% to 32% but the difference was not statistically significant. However, density of microfilaraemia decreased significantly from 170 to 10 mf/ml. Biannual mass treatment with DEC significantly reduced vector infection rates and transmission intensity on Lihir.

Towards eliminating lymphatic filariasis in Papua New Guinea: impact of annual single-dose mass treatment on transmission of Wuchereria bancrofti in East Sepik Province.

The impact of annual single-dose community-wide treatment on the transmission of Wuchereria bancrofti was investigated in 5 villages in the East Sepik Province where pretreatment prevalence of microfilaraemia ranged from 34% to 73%. Anopheles punctulatus and An. koliensis were the only carriers of the parasite. 3 villages received diethylcarbamazine citrate (DEC) in combination with ivermectin (IVR) and 2 received DEC alone. The rate and intensity of microfilaraemia were both reduced in all 5 villages. Reduction in prevalence was between 43% and 67% in the DEC+IVR study villages and between 24% and 27% in the DEC alone villages. Density was reduced by between 81% and 95% in the DEC+IVR villages and between 69% and 74% in the DEC alone villages. Breaks in perennial transmission (failure to detect infective mosquitoes in four or more consecutive monthly collections) occurred in all 3 communities treated with DEC+IVR. Transmission was almost completely interrupted in 2 villages, where infective mosquitoes were not detected during 11 of the 12 months following treatment. We concluded that repeated annual single-dose community-wide treatment with DEC+IVR could lead to complete interruption of transmission and ultimately elimination of lymphatic filariasis.