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Objective: To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response., Introduction and Methods: The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report., Results: We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB deaths. All the targets set at the 2018 United Nations High Level Meeting on TB were off track., Interpretation and Conclusion: The sub-optimal global performance on achieving TB control targets in 2020 is attributed to the on-going COVID-19 pandemic, however, TB programs were already off track well before the onset of the pandemic, suggesting that the pandemic amplified an already fragile global TB response. We emphasize that ending the global TB epidemic will require bold leadership, optimization of existing interventions, widespread coverage, addressing social determinants of TB and importantly mobilization of adequate funding required for TB care and prevention., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The prevalence of diseases other than TB detected during chest X-ray (CXR) screening is unknown in sub-Saharan Africa. This represents a missed opportunity for identification and treatment of potentially significant disease. Our aim was to describe and quantify non-TB abnormalities identified by TB-focused CXR screening during the 2016 Kenya National TB Prevalence Survey., Methods: We reviewed a random sample of 1140 adult (≥15 years) CXRs classified as 'abnormal, suggestive of TB' or 'abnormal other' during field interpretation from the TB prevalence survey. Each image was read (blinded to field classification and study radiologist read) by two expert radiologists, with images classified into one of four major anatomical categories and primary radiological findings. A third reader resolved discrepancies. Prevalence and 95% CIs of abnormalities diagnosis were estimated., Findings: Cardiomegaly was the most common non-TB abnormality at 259 out of 1123 (23.1%, 95% CI 20.6% to 25.6%), while cardiomegaly with features of cardiac failure occurred in 17 out of 1123 (1.5%, 95% CI 0.9% to 2.4%). We also identified chronic pulmonary pathology including suspected COPD in 3.2% (95% CI 2.3% to 4.4%) and non-specific patterns in 4.6% (95% CI 3.5% to 6.0%). Prevalence of active-TB and severe post-TB lung changes was 3.6% (95% CI 2.6% to 4.8%) and 1.4% (95% CI 0.8% to 2.3%), respectively., Interpretation: Based on radiological findings, we identified a wide variety of non-TB abnormalities during population-based TB screening. TB prevalence surveys and active case finding activities using mass CXR offer an opportunity to integrate disease screening efforts., Funding: National Institute for Health Research (IMPALA-grant reference 16/136/35)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Despite high tuberculosis (TB) treatment success rate, treatment adherence is one of the major obstacles to tuberculosis control in Kenya. Our objective was to identify patient-related factors that were associated with time to TB treatment interruption and the geographic distribution of the risk of treatment interruption by county. Data of new and retreatment patients registered in TIBU, a Kenyan national case-based electronic data recording system, between 2013 and 2014 was obtained. Kaplan-Meier curves and log rank tests were used to assess the adherence patterns. Mixed-effects Cox proportional hazards modeling was used for multivariate analysis. Records from 90,170 patients were included in the study. The cumulative incidence of treatment interruption was 4.5% for new patients, and 8.5% for retreatment patients. The risk of treatment interruption was highest during the intensive phase of treatment. Having previously been lost to follow-up was the greatest independent risk factor for treatment interruption (HR: 4.79 [3.99, 5.75]), followed by being HIV-positive not on ART (HR: 1.96 [1.70, 2.26]) and TB relapse (HR: 1.70 [1.44, 2.00]). Male and underweight patients had high risks of treatment interruption (HR: 1.46 [1.35, 1.58]; 1.11 [1.03, 1.20], respectively). High rates of treatment interruption were observed in counties in the central part of Kenya while counties in the northeast had the lowest risk of treatment interruption. A better understanding of treatment interruption risk factors is necessary to improve adherence to treatment. Interventions should focus on patients during the intensive phase, patients who have previously been lost to follow-up, and promotion of integrated TB and HIV services among public and private facilities., Competing Interests: The authors have declared that no competing interests exist.

Background: Schistosomiasis is a debilitating neglected tropical disease that infects over 200 million people worldwide. To combat this disease, in 2012, the World Health Organization announced a goal of reducing and eliminating transmission of schistosomes. Current control focuses primarily on mass drug administration (MDA). Therefore, we monitored transmission of Schistosoma mansoni via fecal egg counts and genetic markers in a typical school based MDA setting to ascertain the actual impacts of MDA on the targeted schistosome population., Methods: For 4 years, we followed 67 children enrolled in a MDA program in Kenya. Infection status and egg counts were measured each year prior to treatment. For 15 of these children, for which there was no evidence of acquired resistance, meaning they became re-infected following each treatment, we collected microsatellite genotype data from schistosomes passed in fecal samples as a representation of the force of transmission between drug treatments. We genotyped a total of 4938 parasites from these children, with an average of 329.2 parasites per child for the entire study, and an average of 82.3 parasites per child per annual examination. We compared prevalence, egg counts, and genetic measures including allelic richness, gene diversity (expected heterozygosity), adult worm burdens and effective number of breeders among time points to search for evidence for a change in transmission or schistosome populations during the MDA program., Findings: We found no evidence of reduced transmission or schistosome population decline over the course of the program. Although prevalence declined in the 67 children as it did in the overall program, reinfection rates were high, and for the 15 children studied in detail, schistosome egg counts and estimated adult worm burdens did not decline between years 1 and 4, and genetic diversity increased over the course of drug treatment., Interpretation: School based control programs undoubtedly improve the health of individuals; however, our data show that in an endemic area, such a program has had no obvious effect on reducing transmission or of significantly impacting the schistosome population as sampled by the children we studied in depth. Results like these, in combination with other sources of information, suggest more integrated approaches for interrupting transmission and significantly diminishing schistosome populations will be required to achieve sustainable control.

Recent schistosomiasis control efforts in sub-Saharan Africa have focused nearly exclusively on treatment of humans with praziquantel. However, the extent to which wild mammals act as reservoirs for Schistosoma mansoni and therefore as sources of renewed transmission following control efforts is poorly understood. With the objective to study the role of small mammals as reservoir hosts, 480 animals belonging to 9 rodent and 1 insectivore species were examined for infection with schistosomes in Kisumu, in the Lake Victoria Basin, Kenya. Animals were collected from 2 sites: near the lakeshore and from Nyabera Marsh draining into the lake. A total of 6.0% of the animals captured, including 5 murid rodent species and 1 species of shrew (Crocidura olivieri) were infected with schistosomes. Four schistosome species were recovered and identified using cox1 DNA barcoding: S. mansoni, S. bovis, S. rodhaini and S. kisumuensis, the latter of which was recently described from Nyabera Marsh. Schistosoma mansoni and S. rodhaini were found infecting the same host individual (Lophuromys flavopunctatus), suggesting that this host species could be responsible for the production of hybrid schistosomes found in the area. Although the prevalence of S. mansoni infection in these reservoir populations was low (1.5%), given their potentially vast population size, their impact on transmission needs further study. Reservoir hosts could perpetuate snail infections and favour renewed transmission to humans once control programmes have ceased.

A recently developed high-throughput technique that allows multi-locus microsatellite analysis of individual miracidia of Schistosoma mansoni was used to assess the levels of genetic diversity and population structure in 12 infrapopulations of the parasite, each infrapopulation derived from an infected school child from the Mwea area, central Kenya. The mean number of alleles per locus was in the range 8.22-10.22, expected heterozygosity in Hardy-Weinberg equilibrium was 0.68-0.70, and pairwise F(ST) values ranged from 0.16% to 3.98% for the 12 infrapopulations. Although the genetic diversity within each infrapopulation of S. mansoni in this area was generally high, low levels of genetic structure were observed, suggestive of high levels of gene flow among infrapopulations. Private alleles were found in 8 of the 12 infrapopulation, the highest number of private alleles recorded per infrapopulation was 3. Our data suggest that the level of gene flow among infrapopulations of S. mansoni in Mwea is extremely high, thus providing opportunity for spread of rare alleles, including those that may confer character traits such as drug resistance and virulence.

Schistosoma kisumuensis n. sp. is described based on 6 adult males and 2 adult females collected from the circulatory system of 3 murid rodent species, Pelomys isseli, Mastomys natalensis, and Dasymys incomtus. Specimens were collected from a single location, Nyabera Swamp, in Kisumu, Kenya in the Lake Victoria Basin. This new species is morphologically similar to members of the S. haematobium group, currently represented by 8 species parasitizing artiodactyls and primates, including humans. Schistosoma kisumuensis differs from these species by producing relatively small Schistosoma intercalatum-like eggs (135.2 x 52.9 microm) with a relatively small length to width ratio (2.55). Comparison of approximately 3000-base-pair sequences of nuclear rDNA (partial 28S) and mtDNA (partial cox1, nad6, 12S) strongly supports the status of S. kisumuensis as a new species and as a sister species of S. intercalatum. The cox1 genetic distance between these two species (6.3%) is comparable to other pairwise comparisons within the S. haematobium group. Separation of the Congo River and Lake Victoria drainage basins is discussed as a possible factor favoring the origin of this species.

Hybridization and introgression can have important consequences for the evolution, ecology and epidemiology of pathogenic organisms. We examined the dynamics of hybridization between a trematode parasite of humans, Schistosoma mansoni, and its sister species, S. rodhaini, a rodent parasite, in a natural hybrid zone in western Kenya. Using microsatellite markers, rDNA and mtDNA, we showed that hybrids between the two species occur in nature, are fertile and produce viable offspring through backcrosses with S. mansoni. Averaged across collection sites, individuals of hybrid ancestry comprised 7.2% of all schistosomes collected, which is a large proportion given that one of the parental species, S. rodhaini, comprised only 9.1% of the specimens. No F1 individuals were collected and all hybrids represented backcrosses with S. mansoni that were of the first or successive generations. The direction of introgression appears highly asymmetric, causing unidirectional gene flow from the rodent parasite, S. rodhaini, to the human parasite, S. mansoni. Hybrid occurrence was seasonal and most hybrids were collected during the month of September over a 2-year period, a time when S. rodhaini was also abundant. We also examined the sex ratios and phenotypic differences between the hybrids and parental species, including the number of infective stages produced in the snail host and the time of day the infective stages emerge. No statistical differences were found in any of these characteristics, and most of the hybrids showed an emergence pattern similar to that of S. mansoni. One individual, however, showed a bimodal emergence pattern that was characteristic of both parental species. In conclusion, these species maintain their identity despite hybridization, although introgression may cause important alterations of the biology and epidemiology of schistosomiasis in this region.

Genetic diversity and population structure of seven populations of Schistosoma mansoni sampled in Kenya were assessed using five microsatellite markers. The mean number of alleles per locus, expected heterozygosity in Hardy-Weinberg equilibrium and pairwise F(ST) values ranged from 5.2 to 10.7, 0.5-0.8 and 3.6-27.3%, respectively. These data reveal that S. mansoni populations in Kenyan have relatively high levels of genetic diversity and is significantly differentiated. Our data combined with information on biogeography support the hypothesis that the strong genetic structure in Kenyan schistosomes is as a result of limited gene flow and large population sizes. Resistance to anthelminthics has not been reported among the Kenyan schistosomes, we hypothesize that this is probably due to the very little gene flow among populations, thereby limiting opportunities for the spread of rare alleles that might confer resistance to the drugs.

Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.

Experimental crosses between Schistosoma mansoni and S. rodhaini have shown that hybrid offspring are viable, yet, until now, no naturally occurring hybrid has been identified. A collection of freshwater snails from Nyamlebi-Ngoma, Ukerewe Island, Lake Victoria, Tanzania, yielded a mixed infection within a single Biomphalaria sudanica of S. mansoni females and S. mansoni-S. rodhaini hybrid males. The hybrids were identified using deoxyribonucleic acid (DNA) sequences. Mitochondrial DNA 16S and 12S sequences of the hybrids match those of S. mansoni, whereas their nuclear ribosomal DNA ITS1 and ITS2 sequences match those of S. rodhaini. The identification of hybrids in Tanzania highlights the possibility that the genetic identity of either parasite species might be modified by introgression.

The Louisiana red swamp crayfish, Procambarus clarkii, which was introduced into east Africa in the 1950s or 1960s, has since widely dispersed. Previous work by our group has shown that P. clarkii can reduce populations of the molluscan intermediate hosts of human schistosomes through predatory and competitive interactions. Here, we investigate whether crayfish can reduce populations of Bulinus africanus and consequently, Schistosoma haematobium prevalence in school children. Children from 6 primary schools in the Machakos and Kitui Districts of Kenya were selected for study. Schools were divided into 3 experimental-control pairs. At experimental schools, crayfish were introduced into nearby aquatic habitats harboring Bulinus africanus snails and serving as S. haematobium transmission sites. Snail habitats near control schools did not receive crayfish. Six months after crayfish introduction, all infected children were treated with praziquantel. Children were then monitored quarterly for 2 years, at which time infection and reinfection rates were compared statistically between the paired schools. In one such pair, crayfish failed to establish, resulting in neither snail control nor a reduction in transmission. At the second pair of schools, the numbers of snails were decreased by the presence of crayfish, but a clear difference in infection rates in children could not be detected, primarily because drought conditions kept overall transmission rates low. At the third school pair, crayfish established well in experimental habitats, snail numbers decreased precipitously, and children at the experimental school were significantly less likely to acquire S. haematobium infections than children at the control school. Our results indicate that under certain environmental circumstances, P. clarkii exerts a significant impact on the transmission of human schistosomiasis in Kenya. Important questions remain regarding the impact of P. clarkii on Kenyan freshwater ecosystems, not the least of which is its potential to significantly influence the epidemiology of schistosomiasis in east Africa.

Laboratory experiments lasting 1-3 days were conducted in 10-liter glass aquaria to evaluate the ability of the Louisiana red swamp crawfish (Procambarus clarkii [Decapoda: Cambaridae]) to consume the aquatic forms of mosquitoes. With Anopheles gambiae as the target species, significantly fewer mosquito larvae or pupae survived in the presence of either juvenile or adult crawfish, relative to conditions without crawfish, regardless of whether crawfish had alternative food or not. When alternative food was excluded, juvenile and adult crawfish had a comparable ability to consume mosquito larvae. However, when alternative food was available, adult crawfish consumed significantly fewer mosquito larvae than did juveniles. In the case of pupae, juvenile crawfish consumed significantly more mosquito pupae than did the adults when alternative food was excluded. No significant difference, relative to controls, was found in the proportion of mosquito pupae surviving when adult crawfish had alternative food. Results of the present study show that P. clarkii has the ability to consume the aquatic forms of anopheline mosquitoes and, therefore, may have an impact on populations of pathogen-transmitting mosquitoes in an area of Kenya where the crawfish has become common.

Adults of the African ampullariid snail Pila ovata were examined for their ability to control laboratory populations of the pulmonate snail Biomphalaria pfeifferi, a widespread, intermediate host of the human pathogen Schistosoma mansoni in sub-Saharan Africa. In a 6-week experiment conducted in large (100 x 60 x 60 cm) outdoor tanks containing floating macrophytes (Nymphaea caerula) and initially set up with one adult ampullariid for every three adult pulmonates, the numbers of B. pfeifferi egg masses were always about half those in similar tanks without P. ovata. Although, by week 6, the numbers of B. pfeifferi in the control tanks (without ampullariids) had increased 5-fold, from an initial mean of 30 snails/tank, there was no significant increase in the numbers of B. pfeifferi in the experimental tanks (containing ampullariids). Results of experiments conducted in indoor glass aquaria indicated that adult P. ovata rapidly attacked egg masses or neonates (< 2.5 mm shell diameter) of B. pfeifferi but had no effect on the adults. The adult ampullariids also significantly decreased cover by floating macrophytes over a 6-week period compared with that in similar but ampullariid-free aquaria. This decrease in plant cover is relevant to biological control of the schistosome vectors as macrophytes serve as food, shelter and oviposition sites for pulmonate snails. The present result indicate the ability of P. ovata to inhibit multiplication of B. pfeifferi populations, at least under laboratory conditions, both directly, through predation, and indirectly, by competition for resources. Pila ovata may therefore prove useful in the biological control of medically important, pulmonate snails.

Aqueous suspensions of powder of sun- or freeze-dried berries of the plant Solanum aculeatum (Family Solanaceae), indigenous in Kenya, were tested for molluscicidal activity against Biomphalaria pfeifferi, Bulinus globosus and Lymnaea natalensis under laboratory conditions. One hundred or 50 mg powder L-1 of sun- or freeze-dried berries killed over 60% of the test B. pfeifferi, Bul. globosus and L. natalensis. Whereas 25 mg L-1 of the sun dried material killed less than 60% of the test snails, similar concentrations of the freeze dried molluscicide produced 60-80% mortality in the snails, under similar conditions. Using L. natalensis as the target snail, it was shown that the freeze dried material was more potent than the freeze-dried berries of S. incanum, S. nigrum or leaves of Polygonum senegalensis (Family Polygonaceae), all present in Kenya, and known to possess molluscicidal properties. The powdered material retained molluscicidal activity even after several months storage at room temperature. These findings suggest that S. aculeatum is a potent plant molluscicide, and has the potential for the control of vectors of schistosomiasis and fascioliasis in Kenya.